Submissions for variant NM_002471.4(MYH6):c.3979-7dup

gnomAD frequency: 0.00208  dbSNP: rs545343612

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000155860	SCV000205571	benign	not specified	2013-06-17	criteria provided, single submitter	clinical testing	3979-7_3979-6insT in intron 28 of MYH6: This variant is not expected to have cli nical significance because it has been identified in 1.9% (78/4188) of African A merican chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washing ton.edu/EVS/).
Invitae	RCV000470424	SCV000557898	benign	Hypertrophic cardiomyopathy 14	2024-01-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000155860	SCV000919827	benign	not specified	2018-05-30	criteria provided, single submitter	clinical testing	Variant summary: MYH6 c.3979-7dupT 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. 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 0.0018 in 205828 control chromosomes in the gnomAD database, including 1 homozygotes. The observed variant frequency is approximately 72 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 benign. To our knowledge, no occurrence of c.3979-7dupT in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
GeneDx	RCV001573632	SCV001915096	benign	not provided	2016-11-15	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798517	SCV002043189	benign	Cardiomyopathy	2019-10-10	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001573632	SCV002047910	likely benign	not provided	2023-10-09	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001573632	SCV004129068	benign	not provided	2022-06-01	criteria provided, single submitter	clinical testing	MYH6: BS1, BS2
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001573632	SCV001799805	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000155860	SCV001919516	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001573632	SCV001930716	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001573632	SCV001958745	likely benign	not provided		no assertion criteria provided	clinical testing