ClinVar Miner

Submissions for variant NM_002471.3(MYH6):c.3979-7del (rs397516766)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000037492 SCV000061150 benign not specified 2015-04-01 criteria provided, single submitter clinical testing c.3979-7delT in intron 28 of MYH6: This variant is not expected to have clinical significance because it has been identified in 8.5% (304/3564) of African chrom osomes, including 4 homozygotes, by the Exome Aggregation Consortium (ExAC, http ://exac.broadinstitute.org; dbSNP rs397516766).
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000037492 SCV000228710 benign not specified 2014-12-16 criteria provided, single submitter clinical testing
Invitae RCV000230041 SCV000287415 benign Familial hypertrophic cardiomyopathy 14 2019-12-18 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000406134 SCV000385612 likely benign Hypertrophic cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000289273 SCV000385613 likely benign Atrial septal defect 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000344303 SCV000385614 likely benign Dilated Cardiomyopathy, Dominant 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000037492 SCV000565685 benign not specified 2016-12-30 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.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000037492 SCV001159514 benign not specified 2018-10-23 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000037492 SCV001372299 benign not specified 2020-06-15 criteria provided, single submitter clinical testing Variant summary: MYH6 c.3979-7delT alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0032 in 184810 control chromosomes, predominantly at a frequency of 0.08 within the African or African-American subpopulation in the gnomAD database, including 6 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 3200 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 found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.3979-7delT in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Five 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 (n=4)/likely benign (n=1). Based on the evidence outlined above, the variant was classified as benign.

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