ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.1132G>A (p.Gly378Ser)

gnomAD frequency: 0.00014  dbSNP: rs148962966
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000154766 SCV000204446 likely benign not specified 2013-12-26 criteria provided, single submitter clinical testing Gly378Ser in exon 12 of MYH6: This variant is not expected to have clinical sign ificance because it has been identified in 1.0% (6/572) of Asian chromosomes by the 1000 Genomes Project (dbSNP rs148962966). Gly378Ser in exon 12 of MYH6 (rs1 48962966; allele frequency = 1.0%, 6/572)
Ambry Genetics RCV000241733 SCV000319653 likely benign Cardiovascular phenotype 2017-12-12 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae RCV000464311 SCV000557903 benign Hypertrophic cardiomyopathy 14 2024-01-17 criteria provided, single submitter clinical testing
GeneDx RCV001697081 SCV000718668 likely benign not provided 2021-05-26 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001170246 SCV001332806 likely benign Cardiomyopathy 2017-12-27 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000154766 SCV001432004 benign not specified 2020-08-17 criteria provided, single submitter clinical testing Variant summary: MYH6 c.1132G>A (p.Gly378Ser) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00088 in 251172 control chromosomes, including 1 homozygote (gnomAD). The variant was found at a frequency of 0.006 within the East Asian subpopulation, this frequency is approximately 230-fold of the estimated maximal expected allele frequency for a pathogenic variant in MYH6 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is a benign polymorphism. To our knowledge, no occurrence of c.1132G>A in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign (1x) / likely benign (3x). Based on the evidence outlined above, the variant was classified as benign.
Genetics and Genomics Program, Sidra Medicine RCV001293155 SCV001434152 uncertain significance Hypertrophic cardiomyopathy criteria provided, single submitter research
Genetics and Genomics Program, Sidra Medicine RCV001293167 SCV001434164 uncertain significance Primary dilated cardiomyopathy criteria provided, single submitter research
Clinical Genetics, Academic Medical Center RCV000154766 SCV001925762 benign not specified no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001697081 SCV001973843 likely benign not provided no assertion criteria provided clinical testing

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