ClinVar Miner

Submissions for variant NM_002471.3(MYH6):c.3199A>G (p.Ser1067Gly) (rs145508517)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000172562 SCV000054813 likely benign not provided 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000037470 SCV000061128 uncertain significance not specified 2017-02-22 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Ser1067Gly va riant in MYH6 has been identified by our laboratory in 1 Hispanic individual wit h HCM, but did NOT segregate with disease in 1 affected relative. This variant w as identified in 0.1% (11/10406) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs145508517). Computat ional prediction tools and conservation analysis do not provide strong support f or or against an impact to the protein. This variant was identified in ClinVar ( Variant ID:44477). In summary, while the clinical significance of the p.Ser1067G ly variant is uncertain, its frequency and non-segregation suggests that it is m ore likely to be benign.
Illumina Clinical Services Laboratory,Illumina RCV000276495 SCV000385684 uncertain significance Dilated Cardiomyopathy, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000333921 SCV000385685 uncertain significance Atrial septal defect 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000386021 SCV000385686 uncertain significance Hypertrophic cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000037470 SCV000917834 likely benign not specified 2018-05-29 criteria provided, single submitter clinical testing Variant summary: MYH6 c.3199A>G (p.Ser1067Gly) results in a non-conservative amino acid change located in the Myosin tail domain of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant frequency in the gnomAD database was 0.000097, but was observed predominantly in the African subpopulation at a frequency of 0.00099. This frequency within African control individuals in the gnomAD database is approximately 40 fold above 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 found primarily in populations of African origin. c.3199A>G has been reported in the literature, however, this report does not provide unequivocal conclusions about association of the variant with Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and both classified the variant as uncertain significance, although the summary evidence provided by one of them suggests a benign etiology. Based on the evidence outlined above, the variant was classified as likely benign.
Invitae RCV000172562 SCV001006023 likely benign not provided 2019-02-21 criteria provided, single submitter clinical testing

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