Submissions for variant NM_002471.4(MYH6):c.3195G>C (p.Gln1065His)

gnomAD frequency: 0.00015  dbSNP: rs267606904

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000171836	SCV000054814	uncertain significance	Hypertrophic cardiomyopathy	2018-04-05	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037469	SCV000061127	uncertain significance	not specified	2015-03-18	criteria provided, single submitter	clinical testing	The p.Gln1065His variant in MYH6 has been reported in 2 individuals with HCM (Ca rniel 2005, Ng 2013) and has been identified by our laboratory in 1 individual w ith HCM and 1 individual with LVNC. This variant has also been identified in 0.1 % (11/8654) of East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs267606904). Computational prediction to ols and conservation analysis do not provide strong support for or against an im pact to the protein although the variant amino acid is present in several specie s (birds), raising the possibility that the change may be tolerated. In summary, the clinical significance of the p.Gln1065His variant is uncertain.
Invitae	RCV000015212	SCV000287403	likely benign	Hypertrophic cardiomyopathy 14	2022-12-18	criteria provided, single submitter	clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000414926	SCV000492555	uncertain significance	Primary dilated cardiomyopathy; Migraine; Hemiplegia	2014-11-24	criteria provided, single submitter	clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000845359	SCV000987413	uncertain significance	not provided		criteria provided, single submitter	clinical testing
Mendelics	RCV000015212	SCV001139404	uncertain significance	Hypertrophic cardiomyopathy 14	2019-05-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000845359	SCV001785495	uncertain significance	not provided	2023-07-26	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 23861362, 28518168, 15998695, 34426522, 34697898, 35621855, 34045587, 27788187)
Ambry Genetics	RCV002321482	SCV002609680	likely benign	Cardiovascular phenotype	2019-03-18	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
OMIM	RCV000015212	SCV000035469	pathogenic	Hypertrophic cardiomyopathy 14	2005-07-05	no assertion criteria provided	literature only
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000845359	SCV001932034	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000845359	SCV001959438	likely benign	not provided		no assertion criteria provided	clinical testing