Submissions for variant NM_002471.4(MYH6):c.1071C>T (p.Ile357=)

gnomAD frequency: 0.00309  dbSNP: rs58131640

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037436	SCV000061094	benign	not specified	2012-01-09	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000226540	SCV000287391	benign	Hypertrophic cardiomyopathy 14	2024-01-22	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000037436	SCV000338589	benign	not specified	2016-01-05	criteria provided, single submitter	clinical testing
GeneDx	RCV000037436	SCV000524264	benign	not specified	2016-12-05	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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769427	SCV000900820	benign	Cardiomyopathy	2015-12-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000037436	SCV000917832	benign	not specified	2018-05-08	criteria provided, single submitter	clinical testing	Variant summary: MYH6 c.1071C>T alters a conserved nucleotide resulting in a synonymous change. 5/5 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 0.00086 in 277076 control chromosomes, predominantly at a frequency of 0.0096 within the African subpopulation in the gnomAD database, including 4 homozygotes. The observed variant frequency within African control individuals in the gnomAD database is approximately 384 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 origin. To our knowledge, no occurrence of c.1071C>T 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 (3 benign, 1 VUS). Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001811258	SCV002047943	benign	not provided	2020-10-20	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002496586	SCV002810258	likely benign	Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to	2022-02-14	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001811258	SCV005232871	benign	not provided		criteria provided, single submitter	not provided
Clinical Genetics, Academic Medical Center	RCV000037436	SCV001923516	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000037436	SCV001972904	benign	not specified		no assertion criteria provided	clinical testing