Submissions for variant NM_016239.4(MYO15A):c.823G>C (p.Gly275Arg)

gnomAD frequency: 0.00158  dbSNP: rs183969516

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000724577	SCV000227444	uncertain significance	not provided	2018-05-14	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000213326	SCV000272113	uncertain significance	not specified	2018-03-01	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The p.Gly275Arg var iant in MYO15A has been previously identified in 4 individuals with hearing loss , but none of these individuals had a pathogenic variant affecting the other cop y of the MYO15A and an alternate cause of hearing loss was identified in 2 (LMM data, Shearer 2013). This variant has been identified in 0.2% (123/63950) of Eur opean chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broa dinstitute.org; dbSNP rs183969516) and is reported in ClinVar (Variation ID:1953 11). Computational prediction tools and conservation analysis suggest that the p .Gly275Arg variant may not impact the protein, though this information is not pr edictive enough to rule out pathogenicity. In summary, while the clinical signif icance of the p.Gly275Arg variant is uncertain, its frequency suggests that it i s more likely to be benign. ACMG/AMP Criteria applied: BP4.
Illumina Laboratory Services, Illumina	RCV001126235	SCV001285399	uncertain significance	Autosomal recessive nonsyndromic hearing loss 3	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV000724577	SCV001891061	benign	not provided	2020-03-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000724577	SCV002150439	benign	not provided	2024-01-29	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000724577	SCV004142387	likely benign	not provided	2022-10-01	criteria provided, single submitter	clinical testing	MYO15A: BP4
PreventionGenetics, part of Exact Sciences	RCV003937587	SCV004752384	likely benign	MYO15A-related disorder	2023-04-20	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).