ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.77C>T (p.Ala26Val) (rs186964570)

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Total submissions: 17
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000618296 SCV000740061 likely benign Cardiovascular phenotype 2016-10-27 criteria provided, single submitter clinical testing
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000148713 SCV000050867 benign Primary familial hypertrophic cardiomyopathy 2013-06-24 criteria provided, single submitter research
CSER_CC_NCGL; University of Washington Medical Center RCV000148713 SCV000190443 uncertain significance Primary familial hypertrophic cardiomyopathy 2014-06-01 no assertion criteria provided research
ClinGen Inherited Cardiomyopathy Variant Curation Expert Panel, RCV000758056 SCV000564467 benign Cardiomyopathy 2016-12-15 reviewed by expert panel curation The filtering allele frequency of the c.77C>T (p.Ala26Val) variant in the MYH7 gene is 0.55% (60/8646) of East Asian chromosomes by the Exome Aggregation Consortium (http://exac.broadinstitute.org), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Inherited Cardiomyopathy Expert Panel (BA1; PMID:29300372).
Color RCV000758056 SCV000903190 benign Cardiomyopathy 2018-07-09 criteria provided, single submitter clinical testing
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000168831 SCV000296899 uncertain significance Familial hypertrophic cardiomyopathy 1 2015-10-12 criteria provided, single submitter clinical testing
GeneDx RCV000036003 SCV000208658 likely benign not specified 2015-08-11 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Clinical Services Laboratory,Illumina RCV000377499 SCV000386353 likely benign Scapuloperoneal myopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000264317 SCV000386354 likely benign Myosin storage myopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000319538 SCV000386355 likely benign Dilated Cardiomyopathy, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000374158 SCV000386356 likely benign Myopathy, distal, 1 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000279740 SCV000386357 likely benign Hypertrophic cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000334846 SCV000386358 likely benign Left ventricular noncompaction cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000279740 SCV000557966 benign Hypertrophic cardiomyopathy 2017-12-14 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000036003 SCV000059655 likely benign not specified 2012-12-12 criteria provided, single submitter clinical testing Ala26Val in exon 3 of MYH7: This variant has been reported in 10 HCM probands of Asian descent and was absent from 832 race-matched control chromosomes (Konno 2 005, Liu 2005, Song 2005, Wang 2009). However, one of the probands had another p athogenic HCM variant on the same copy of the gene which segregated with all 8 a ffected family members (Wang 2009). Although segregation in 3 family members was observed in one other family, an additional 5 individuals had the variant witho ut disease including three over age 70 (Liu 2005). Our laboratory has observed t his variant in one HCM proband and one DCM proband, neither with a family histor y of disease, out of over 3500 cases tested (1/215 Asian probands). This variant has been observed in 1.5% (6/388) of Chinese chromosomes in a broad population (1000 Genomes project, rs186964570), suggesting that it is not disease causing i n isolation. Computational analyses (biochemical amino acid properties, conserva tion, AlignGVGD, PolyPhen2, and SIFT) suggest that the Ala26Val variant is less likely to impact the protein, particularly given the lack of evolutionary conser vation in some mammalian species. In summary, the high frequency of this variant in Asians and poor evolutionary conservation suggest that this variant is benig n but additional data is needed to establish this with certainty. A modifying e ffect cannot be ruled out.
Soonchunhyang University Bucheon Hospital,Soonchunhyang University Medical Center RCV000168831 SCV000267409 uncertain significance Familial hypertrophic cardiomyopathy 1 2016-03-18 criteria provided, single submitter reference population
Stanford Center for Inherited Cardiovascular Disease,Stanford University RCV000721101 SCV000280379 likely benign not provided 2016-08-22 no assertion criteria provided provider interpretation Given the allele frequency in East Asians in ExAC, we consider this variant likely benign (AF 0.0069).

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