Submissions for variant NM_002471.4(MYH6):c.4206C>T (p.Ala1402=)

gnomAD frequency: 0.00728  dbSNP: rs111638554

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037499	SCV000061157	benign	not specified	2012-07-06	criteria provided, single submitter	clinical testing	Ala1402Ala in Exon 30 of MYH6: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence and has been identified in 2.8% (104/3738) of Afr ican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs111638554).
Labcorp Genetics (formerly Invitae), Labcorp	RCV001084998	SCV000287423	benign	Hypertrophic cardiomyopathy 14	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000254156	SCV000318582	benign	Cardiovascular phenotype	2015-07-15	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590525	SCV000697927	benign	not provided	2017-06-26	criteria provided, single submitter	clinical testing	Variant summary: The MYH6 c.4206C>T (p.Ala1402Ala) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 266/121350 control chromosomes (2 homozygotes) at a frequency of 0.002192, which is approximately 88 times the estimated maximal expected allele frequency of a pathogenic MYH6 variant (0.000025), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. Taken together, this variant is classified as benign.
GeneDx	RCV000037499	SCV000719327	benign	not specified	2017-04-05	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	RCV000770437	SCV000901880	benign	Cardiomyopathy	2016-06-17	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000590525	SCV001471953	benign	not provided	2022-12-21	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002504893	SCV002805216	benign	Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to	2022-01-05	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000590525	SCV005232855	benign	not provided		criteria provided, single submitter	not provided
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000590525	SCV001743018	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000037499	SCV001919112	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000037499	SCV001965213	benign	not specified		no assertion criteria provided	clinical testing