Clinically relevant variants - identifying, collecting, interpreting, and disseminating: the 2013 annual scientific meeting of the Human Genome Variation Society.


:The dramatic advances in genetic sequencing technologies used in research laboratories are now entering the clinic, and applications of whole-genome and whole-exome sequencing to disease diagnosis, predisposition, and treatment will soon be commonplace. However, the standards and methods for identifying clinically relevant variants are currently being debated and defined. Multiple agencies worldwide have recognized that we have reached an exciting and critical transition point into the clinic, and many important issues are being discussed that impact how genetic variation data in the clinic will be interpreted and used. The 2013 annual scientific meeting of the Human Genome Variation Society (HGVS) had as its main theme the discovery, interpretation, and dissemination of clinically relevant DNA variants. The meeting featured the continuously developing technology of databasing genetic variation and computational tools for allelic variant discovery. Attention was given to curating and integrating these data with clinical findings, including approaches to distinguish between functional alleles underlying clinical phenotypes and benign sequence variants and making data sources interoperable and functional for clinical diagnostic utility, citing examples in specific diseases.


Hum Mutat


Human mutation


Stanley CM,Sunyaev SR,Greenblatt MS,Oetting WS




Has Abstract


2014-04-01 00:00:00












  • Three-Dimensional Model of Human Nicotinamide Nucleotide Transhydrogenase (NNT) and Sequence-Structure Analysis of its Disease-Causing Variations.

    abstract::Defective mitochondrial proteins are emerging as major contributors to human disease. Nicotinamide nucleotide transhydrogenase (NNT), a widely expressed mitochondrial protein, has a crucial role in the defence against oxidative stress. NNT variations have recently been reported in patients with familial glucocorticoid...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Metherell LA,Guerra-Assunção JA,Sternberg MJ,David A

    更新日期:2016-10-01 00:00:00

  • Identification of a novel NOG gene mutation (P35S) in an Italian family with symphalangism.

    abstract::Symphalangism (SYM or SYM1) is an autosomal dominant disorder characterized by multiple joint fusions. The disease is caused by mutations of the NOG gene, that maps to chromosome 17q22. So far, only six independent NOG mutations have been identified. We have analysed an Italian family in which father and son had bilat...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Mangino M,Flex E,Digilio MC,Giannotti A,Dallapiccola B

    更新日期:2002-03-01 00:00:00

  • EIF2S3 Mutations Associated with Severe X-Linked Intellectual Disability Syndrome MEHMO.

    abstract::Impairment of translation initiation and its regulation within the integrated stress response (ISR) and related unfolded-protein response has been identified as a cause of several multisystemic syndromes. Here, we link MEHMO syndrome, whose genetic etiology was unknown, to this group of disorders. MEHMO is a rare X-li...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Skopkova M,Hennig F,Shin BS,Turner CE,Stanikova D,Brennerova K,Stanik J,Fischer U,Henden L,Müller U,Steinberger D,Leshinsky-Silver E,Bottani A,Kurdiova T,Ukropec J,Nyitrayova O,Kolnikova M,Klimes I,Borck G,Bahlo M,

    更新日期:2017-04-01 00:00:00

  • Spectrum of low density lipoprotein receptor mutations in Czech hypercholesterolemic patients.

    abstract::The aim of our study was to define mutations causing familial hypercholesterolemia (FH) phenotype in Czech hypercholesterolemic individuals. A combination of heteroduplex analysis, SSCP, DGGE, DNA sequencing and PCR/restriction analysis was used for this purpose. Molecular searching in the promoter region and coding s...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Kuhrová V,Francová H,Zapletalová P,Freiberger T,Fajkusová L,Hrabincová E,Slováková R,Kozák L

    更新日期:2001-09-01 00:00:00

  • Screening practices for mutations in the CFTR gene ABCC7.

    abstract::Cystic fibrosis transmembrane conductance regulator (CFTR) gene studies are now one of the most frequent activities in clinical molecular genetics laboratories. The number of requests is growing, owing to the increasingly wide range of recognized CFTR gene diseases (cystic fibrosis, congenital bilateral absence of the...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Girodon-Boulandet E,Cazeneuve C,Goossens M

    更新日期:2000-01-01 00:00:00

  • IQSEC2 mutation update and review of the female-specific phenotype spectrum including intellectual disability and epilepsy.

    abstract::The IQSEC2- related disorders represent a spectrum of X-chromosome phenotypes with intellectual disability (ID) as the cardinal feature. Here, we review the increasing number of reported families and isolated cases have been reported with a variety of different pathogenic variants. The spectrum of clinical features is...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Shoubridge C,Harvey RJ,Dudding-Byth T

    更新日期:2019-01-01 00:00:00

  • A new PCR assay useful for screening of FRAXE/FMR2 mental impairment among males.

    abstract::FRAXE (FMR2) is a fragile site associated with mental impairment located in Xq28, 600 kb distal to FRAXA (FMR1), the fragile X syndrome fragile site. The FRAXE mutation is an expansion of a CCG repeat that results in methylation of a nearby CpG island. FRAXE alleles could be divided into four categories: normal (6-30 ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Santos CB,Costa Lima MA,Pimentel MM

    更新日期:2001-08-01 00:00:00

  • Detection of heterozygous deletions and duplications in the MECP2 gene in Rett syndrome by Robust Dosage PCR (RD-PCR).

    abstract::Fifty to eighty percent of Rett syndrome (RTT) cases have point mutations in the gene encoding methyl-CpG-binding protein-2 (MECP2). A fraction of MECP2 negative classical RTT patients has large heterozygous deletions. Robust Dosage PCR (RD-PCR) assays were developed as a rapid, convenient and accurate method to detec...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Shi J,Shibayama A,Liu Q,Nguyen VQ,Feng J,Santos M,Temudo T,Maciel P,Sommer SS

    更新日期:2005-05-01 00:00:00

  • Characterization of seven novel mutations in seven patients with GAMT deficiency.

    abstract::Guanidinoacetate methyltransferase (GAMT) deficiency is an autosomal recessive error of creatine synthesis characterized by cerebral creatine deficiency, accumulation of guanidinoacetate, mental retardation, epilepsy and extrapyramidal signs. So far, six mutations have been identified in seven patients. We investigate...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Item CB,Mercimek-Mahmutoglu S,Battini R,Edlinger-Horvat C,Stromberger C,Bodamer O,Mühl A,Vilaseca MA,Korall H,Stöckler-Ipsiroglu S

    更新日期:2004-05-01 00:00:00

  • MEFV mutations in Behçet's disease.

    abstract::Familial Mediterranean fever (FMF) and Behçet's disease (BD), both inflammatory diseases, are highly prevalent in the Middle Eastern and Mediterranean populations. FMF is a Mendelian autosomic recessive disease linked to MEFV, a gene of unknown function. BD in contrast is a polyfactorial disease associated with the ma...

    journal_title:Human mutation

    pub_type: 杂志文章,多中心研究


    authors: Touitou I,Magne X,Molinari N,Navarro A,Quellec AL,Picco P,Seri M,Ozen S,Bakkaloglu A,Karaduman A,Garnier JM,Demaille J,Koné-Paut I

    更新日期:2000-09-01 00:00:00

  • EYS is a major gene for rod-cone dystrophies in France.

    abstract::Autosomal-recessive retinitis pigmentosa (arRP) was recently associated with mutations in a novel gene EYS, spanning over 2 Mb, making it the largest known gene expressed in the human eye. The purpose of this study was to establish the prevalence and nature of EYS mutations in a clinically well-characterized cohort of...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Audo I,Sahel JA,Mohand-Saïd S,Lancelot ME,Antonio A,Moskova-Doumanova V,Nandrot EF,Doumanov J,Barragan I,Antinolo G,Bhattacharya SS,Zeitz C

    更新日期:2010-05-01 00:00:00

  • Mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) variants in American and Japanese populations.

    abstract::M6P/IGF2R encodes a multifunctional protein involved in lysosomal enzyme trafficking, fetal organogenesis, tumor suppression, and cytotoxic T cell-induced apoptosis. M6P/IGF2R is imprinted and expressed only from the maternally inherited allele in marsupials and rodents. In contrast, humans were initially reported to ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Killian JK,Oka Y,Jang HS,Fu X,Waterland RA,Sohda T,Sakaguchi S,Jirtle RL

    更新日期:2001-01-01 00:00:00

  • Mutation spectrum in patients with Rett syndrome in the German population: Evidence of hot spot regions.

    abstract::Mutations in the MECP2 (Methyl-CpG-binding protein) gene recently have been reported to cause Rett syndrome (RTT), an X-linked dominant neurodevelopmental disease. We investigated 125 sporadic cases of Rett syndrome by direct sequencing. Thirty different mutations were found in 97 patients with Rett syndrome. Seventee...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Laccone F,Huppke P,Hanefeld F,Meins M

    更新日期:2001-03-01 00:00:00

  • The 185delAG mutation (c.68_69delAG) in the BRCA1 gene triggers translation reinitiation at a downstream AUG codon.

    abstract::The 185delAG mutation (c.68_69delAG; ter39) in the BRCA1 gene is a founder Jewish Ashkenazi mutation that is carried by 1% of this population and has been identified in thousands of breast or ovarian cancer patients. We have previously described that transcripts bearing this mutation, as well as transcripts bearing th...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Buisson M,Anczuków O,Zetoune AB,Ware MD,Mazoyer S

    更新日期:2006-10-01 00:00:00

  • p53 website and analysis of p53 gene mutations in human cancer: forging a link between epidemiology and carcinogenesis.

    abstract::The p53 tumor suppressor gene has proven to be one of the genes most often mutated in human cancers. It involves mainly point mutations leading to amino acid substitutions in the central region of the protein which impairs normal functions. Analysis of the mutational events that target the p53 gene has revealed eviden...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Soussi T,Dehouche K,Béroud C

    更新日期:2000-01-01 00:00:00

  • Identification of novel mutations in PEX2, PEX6, PEX10, PEX12, and PEX13 in Zellweger spectrum patients.

    abstract::Mutations in each of the 13 identified human PEX genes are known to cause a peroxisomal biogenesis defect (PBD). Affected patients can be divided into two broad clinical spectra: the Zellweger spectrum, which accounts for about 80% of PBD patients, and the rhizomelia chondrodysplasia punctata (RCDP) spectrum. The clin...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Krause C,Rosewich H,Thanos M,Gärtner J

    更新日期:2006-11-01 00:00:00

  • Identification of 36 novel Jagged1 (JAG1) mutations in patients with Alagille syndrome.

    abstract::Alagille syndrome (AGS) is an autosomal dominant disorder characterized by five major symptoms: cholestasis, vertebral deformity, heart malformations, ocular defects and peculiar facial appearance. The previously described Jagged1 (JAG1) gene on chromosome 20p12 has been identified as being responsible for AGS. JAG1 e...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Röpke A,Kujat A,Gräber M,Giannakudis J,Hansmann I

    更新日期:2003-01-01 00:00:00

  • Identification and computationally-based structural interpretation of naturally occurring variants of human protein C.

    abstract::Protein C (PC) is a key regulator of blood clotting and inflammation. Its inherited deficiency is associated with venous thromboembolism, and recombinant activated PC is currently used to increase survival in severe sepsis. The molecular basis of inherited PC deficiency is heterogeneous. Due to its multiple physiologi...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Rovida E,Merati G,D'Ursi P,Zanardelli S,Marino F,Fontana G,Castaman G,Faioni EM

    更新日期:2007-04-01 00:00:00

  • A novel splice site mutation of the EXT2 gene in a Finnish hereditary multiple exostoses family. Mutations in brief no. 197. Online.

    abstract::Hereditary multiple exostoses is a dominantly inherited disease characterized by multiple benign osteochondromas. The affected individuals have an increased risk of developing sarcoma. A large Finnish family with hereditary multiple exostosis was analyzed to find the disease-causing mutation. Blood samples were obtain...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Wolf M,Hemminki A,Kivioja A,Sistonen P,Kaitila I,Ervasti H,Kinnunen J,Karaharju E,Knuutila S

    更新日期:1998-01-01 00:00:00

  • Welander distal myopathy caused by an ancient founder mutation in TIA1 associated with perturbed splicing.

    abstract::Welander distal myopathy (WDM) is an adult onset autosomal dominant disorder characterized by distal limb weakness, which progresses slowly from the fifth decade. All WDM patients are of Swedish or Finnish descent and share a rare chromosome 2p13 haplotype. We restricted the WDM-associated haplotype followed by whole ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Klar J,Sobol M,Melberg A,Mäbert K,Ameur A,Johansson AC,Feuk L,Entesarian M,Orlén H,Casar-Borota O,Dahl N

    更新日期:2013-04-01 00:00:00

  • Comprehensive profiling of BRCA1 and BRCA2 variants in breast and ovarian cancer in Chinese patients.

    abstract::The identification and interpretation of germline BRCA1/2 variants become increasingly important in breast and ovarian cancer (OC) treatment. However, there is no comprehensive analysis of the germline BRCA1/2 variants in a Chinese population. Here we performed a systematic review and meta-analysis on such variants fr...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Gao X,Nan X,Liu Y,Liu R,Zang W,Shan G,Gai F,Zhang J,Li L,Cheng G,Song L

    更新日期:2020-03-01 00:00:00

  • IL-12Rβ1 deficiency: mutation update and description of the IL12RB1 variation database.

    abstract::IL-12Rβ1 deficiency is an autosomal recessive disorder characterized by predisposition to recurrent and/or severe infections caused by otherwise poorly pathogenic mycobacteria and salmonella. IL-12Rβ1 is a receptor chain of both the IL-12 and the IL-23 receptor and deficiency of IL-12Rβ1 thus abolishes both IL-12 and ...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: van de Vosse E,Haverkamp MH,Ramirez-Alejo N,Martinez-Gallo M,Blancas-Galicia L,Metin A,Garty BZ,Sun-Tan Ç,Broides A,de Paus RA,Keskin Ö,Çağdaş D,Tezcan I,Lopez-Ruzafa E,Aróstegui JI,Levy J,Espinosa-Rosales FJ,Sanal Ö,

    更新日期:2013-10-01 00:00:00

  • Repopulation of rho0 cells with mitochondria from a patient with a mitochondrial DNA point mutation in tRNA(Gly) results in respiratory chain dysfunction.

    abstract::Familial hypertrophic ventricular cardiomyopathy has been demonstrated to be associated with a number of mitochondrial DNA (mtDNA) mutations. A fibroblast cell line carrying a mutation in its mtDNA at position 9997 in the gene encoding tRNA glycine was obtained from a patient with hypertrophic cardiomyopathy. To demon...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Raha S,Merante F,Shoubridge E,Myint AT,Tein I,Benson L,Johns T,Robinson BH

    更新日期:1999-01-01 00:00:00

  • The 2004 Human Genome Variation Society scientific meeting.

    abstract::The Human Genome Variation Society annual scientific meeting was held on 26 October 2004 in Toronto, Canada, and attracted 85 registrants. Meeting participants from 14 countries reported on the recent advances and progress made toward the detection, analysis, and documentation of genetic variation. Reports were made o...

    journal_title:Human mutation



    authors: Oetting WS,Tabone T

    更新日期:2005-08-01 00:00:00

  • Deletions of SCN1A 5' genomic region with promoter activity in Dravet syndrome.

    abstract::Mutations involving the voltage-gated sodium channel alpha(I) gene SCN1A are major genetic causes of childhood epileptic disorders, as typified by Dravet syndrome. Here we investigated the upstream regions of the SCN1A 5' noncoding exons and found two major regions with promoter activity. These two major promoters wer...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Nakayama T,Ogiwara I,Ito K,Kaneda M,Mazaki E,Osaka H,Ohtani H,Inoue Y,Fujiwara T,Uematsu M,Haginoya K,Tsuchiya S,Yamakawa K

    更新日期:2010-07-01 00:00:00

  • Novel CASK mutations in cases with syndromic microcephaly.

    abstract::Mutations in CASK cause a wide spectrum of phenotypes in humans ranging from mild X-linked intellectual disability to a severe microcephaly (MC) and pontocerebellar hypoplasia syndrome. Nevertheless, predicting pathogenicity and phenotypic consequences of novel CASK mutations through the exclusive consideration of gen...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Cristofoli F,Devriendt K,Davis EE,Van Esch H,Vermeesch JR

    更新日期:2018-07-01 00:00:00

  • Maternal MTHFR variant forms increase the risk in offspring of isolated nonsyndromic cleft lip with or without cleft palate.

    abstract::The pathogenesis of cleft lip with or without cleft palate (CL/P) is complex; its onset could be due to the interaction of various genetic and environmental factors. Recently MTHFR functional polymorphisms were found to increase the risk of this common malformation; however, this finding is still debated. We investiga...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Pezzetti F,Martinelli M,Scapoli L,Carinci F,Palmieri A,Marchesini J,Carinci P,Caramelli E,Rullo R,Gombos F,Tognon M

    更新日期:2004-07-01 00:00:00

  • Three novel thiopurine S-methyltransferase allelic variants (TPMT*20, *21, *22) - association with decreased enzyme function.

    abstract::The genetic polymorphism of the thiopurine S-methyltransferase, TPMT, comprises at least 21 alleles causing three distinct drug metabolism phenotypes termed normal/high, intermediate, and deficient methylators. In consequence, adverse drug reactions may occur if standard doses of thiopurines are applied routinely. Gen...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Schaeffeler E,Eichelbaum M,Reinisch W,Zanger UM,Schwab M

    更新日期:2006-09-01 00:00:00

  • Mutations causing Gaucher disease.

    abstract::Glucocerebrosidase is a lysosomal enzyme responsible for hydrolysis of glucosylceramide to ceramide and glucose. Mutations disrupting the function of this enzyme cause autosomal recessive Gaucher disease. This disease is very heterogeneous. The clinical heterogeneity is due to a large number of mutations within the ge...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Horowitz M,Zimran A

    更新日期:1994-01-01 00:00:00

  • Diagnostic exome sequencing to elucidate the genetic basis of likely recessive disorders in consanguineous families.

    abstract::Rare, atypical, and undiagnosed autosomal-recessive disorders frequently occur in the offspring of consanguineous couples. Current routine diagnostic genetic tests fail to establish a diagnosis in many cases. We employed exome sequencing to identify the underlying molecular defects in patients with unresolved but puta...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Makrythanasis P,Nelis M,Santoni FA,Guipponi M,Vannier A,Béna F,Gimelli S,Stathaki E,Temtamy S,Mégarbané A,Masri A,Aglan MS,Zaki MS,Bottani A,Fokstuen S,Gwanmesia L,Aliferis K,Bustamante Eduardo M,Stamoulis G,Psoni S

    更新日期:2014-10-01 00:00:00