Submissions for variant NM_001145809.2(MYH14):c.1034C>G (p.Ser345Cys)

gnomAD frequency: 0.00249  dbSNP: rs35315400

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000155162	SCV000204848	benign	not specified	2012-04-30	criteria provided, single submitter	clinical testing	Ser345Cys in Exon 10 of MYH14: This variant is not expected to have clinical sig nificance because it has been identified in 0.9% (30/3264) of African American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS; dbSNP rs35315400).
GeneDx	RCV000897987	SCV000725926	likely benign	not provided	2020-10-22	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000897987	SCV001042169	benign	not provided	2023-09-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001136432	SCV001296268	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.
Ambry Genetics	RCV002514986	SCV003731135	uncertain significance	Inborn genetic diseases	2022-07-19	criteria provided, single submitter	clinical testing	The c.1010C>G (p.S337C) alteration is located in exon 9 (coding exon 8) of the MYH14 gene. This alteration results from a C to G substitution at nucleotide position 1010, causing the serine (S) at amino acid position 337 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV003927502	SCV004741680	benign	MYH14-related disorder	2019-05-31	no assertion criteria provided	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).