Submissions for variant NM_001145809.2(MYH14):c.3871G>T (p.Val1291Leu)

gnomAD frequency: 0.00024  dbSNP: rs202242879

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000296521	SCV000414430	likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx	RCV000757519	SCV000727739	likely benign	not provided	2021-03-30	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000757519	SCV000885773	likely benign	not provided	2017-07-14	criteria provided, single submitter	clinical testing	The p.Val1250Leu variant (rs202242879) has not been reported in the medical literature, however it has been reported to ClinVar (Variation ID: 329935). This variant is listed in the Genome Aggregation Database (gnomAD) with a frequency in the South Asian population of 0.4 percent (identified on 129 out of 30,394 chromosomes, including 4 homozygotes). The valine at position 1250 is highly conserved considering seven species; however, the physiochemical change to leucine is subtle and unlikely to be disruptive to protein function (Alamut v2.9.0). Altogether, the p.Val1250Leu variant is likely to be benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000757519	SCV002407491	benign	not provided	2023-08-14	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000757519	SCV002543967	benign	not provided	2022-07-01	criteria provided, single submitter	clinical testing	MYH14: BS1, BS2
PreventionGenetics, part of Exact Sciences	RCV003969944	SCV004781638	benign	MYH14-related disorder	2024-06-11	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).