Submissions for variant NM_001145809.2(MYH14):c.2359G>A (p.Glu787Lys)

gnomAD frequency: 0.00002  dbSNP: rs397516628

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037034	SCV000060690	uncertain significance	not specified	2013-02-07	criteria provided, single submitter	clinical testing	The Glu787Lys variant in MYH14 has not been reported in the literature nor previ ously identified by our laboratory. Computational analyses (biochemical amino ac id properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide stro ng support for or against an impact to the protein. Additional data is needed to determine the clinical significance of this variant.
Illumina Laboratory Services, Illumina	RCV000310378	SCV000414402	benign	Autosomal dominant nonsyndromic hearing loss 4A	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV000844487	SCV000986538	benign	not provided	2018-06-04	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.
Invitae	RCV000844487	SCV001121575	benign	not provided	2023-10-13	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003904909	SCV004727779	benign	MYH14-related condition	2023-12-06	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).