Submissions for variant NM_002471.4(MYH6):c.330G>A (p.Ala110=)

gnomAD frequency: 0.00490  dbSNP: rs77679218

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037474	SCV000061132	benign	not specified	2012-03-22	criteria provided, single submitter	clinical testing	Ala110Ala in exon 4 of MYH6: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue, is not located within t he splice consensus sequence, and has been identified in 0.5% (35/7020) of Europ ean American chromosomes from a broad population by the NHLBI Exome Sequencing P roject (http://evs.gs.washington.edu/EVS; dbSNP rs77679218).
Invitae	RCV000233787	SCV000287405	benign	Hypertrophic cardiomyopathy 14	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000245785	SCV000317756	likely benign	Cardiovascular phenotype	2016-06-21	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
GeneDx	RCV000037474	SCV000515728	benign	not specified	2016-11-10	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	RCV000770459	SCV000901902	benign	Cardiomyopathy	2015-11-30	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000037474	SCV000917833	benign	not specified	2017-09-05	criteria provided, single submitter	clinical testing	Variant summary: The MYH6 c.330G>A (p.Ala110Ala) variant involves the alteration of a non-conserved nucleotide causing a synonymous change and 4/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may alter ESE binding. However, these predictions have yet to be confirmed by functional studies. This variant was found in 1116/277156 control chromosomes at a frequency of 0.0040266, which is approximately 161 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 "likely benign/benign." The variant of interest has not, to our knowledge, been reported in affected individuals via publications. Taken together, this variant is classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001528848	SCV001471509	benign	not provided	2020-02-16	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001528848	SCV003917314	benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	MYH6: BP4, BP7, BS1, BS2
PreventionGenetics, part of Exact Sciences	RCV004534786	SCV004736752	benign	MYH6-related disorder	2020-09-17	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528848	SCV001741279	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000037474	SCV001924131	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000037474	SCV001927844	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000037474	SCV001953295	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000037474	SCV001966446	benign	not specified		no assertion criteria provided	clinical testing