Submissions for variant NM_001145809.2(MYH14):c.1919G>A (p.Arg640Gln)

gnomAD frequency: 0.00052  dbSNP: rs199696801

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000214901	SCV000272001	uncertain significance	not specified	2014-12-30	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The p.Arg640Gln var iant in MYH14 has not been previously reported in individuals with hearing loss. This variant has been identified in 0.2% (52/26604) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs 199696801). Although this variant has been seen in the general population, its f requency is not high enough to rule out a pathogenic role. Computational predict ion tools and conservation analyses suggest that the Arg640Gln variant may not i mpact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, while the clinical significance of the p.Arg640Gln va riant is uncertain, these data suggest that it is more likely to be benign.
Illumina Laboratory Services, Illumina	RCV001133104	SCV001292790	likely benign	Autosomal dominant nonsyndromic hearing loss 4A	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001505041	SCV001709932	likely benign	not provided	2024-01-15	criteria provided, single submitter	clinical testing
GeneDx	RCV001505041	SCV001765085	likely benign	not provided	2020-01-14	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 23804846)
CeGaT Center for Human Genetics Tuebingen	RCV001505041	SCV005041518	likely benign	not provided	2024-04-01	criteria provided, single submitter	clinical testing	MYH14: BP4, BS2
PreventionGenetics, part of Exact Sciences	RCV003929907	SCV004738126	likely benign	MYH14-related disorder	2021-11-10	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).