Submissions for variant NM_004999.4(MYO6):c.2982G>A (p.Glu994=)

gnomAD frequency: 0.00487  dbSNP: rs55905349

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038300	SCV000061969	benign	not specified	2012-03-16	criteria provided, single submitter	clinical testing	Glu994Glu in exon 28 of MYO6: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, has been identified in 0.8% (57/7020) of European American chromosomes and 0.16% (6/3738) of African American chromosomes in a br oad population by the NHLBI Exome sequencing project (http://evs.gs.washington.e du/EVS/ ; dbSNP rs55905349) and is reported as benign in one publication (Ahituv 2000).
PreventionGenetics, part of Exact Sciences	RCV000038300	SCV000310771	benign	not specified		criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000038300	SCV000704502	benign	not specified	2016-12-29	criteria provided, single submitter	clinical testing
GeneDx	RCV000873795	SCV000730209	benign	not provided	2019-07-25	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 11167014)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000873795	SCV001015855	benign	not provided	2025-01-29	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000873795	SCV001144695	benign	not provided	2019-07-17	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001164576	SCV001326709	uncertain significance	Autosomal recessive nonsyndromic hearing loss 37	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.
Illumina Laboratory Services, Illumina	RCV001164577	SCV001326710	benign	Autosomal dominant nonsyndromic hearing loss 22	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.
CeGaT Center for Human Genetics Tuebingen	RCV000873795	SCV001747472	likely benign	not provided	2024-09-01	criteria provided, single submitter	clinical testing	MYO6: BP4, BP7, BS2
Ambry Genetics	RCV003242970	SCV003950334	likely benign	Inborn genetic diseases	2023-05-31	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.