Submissions for variant NM_004999.4(MYO6):c.1030G>A (p.Val344Ile)

gnomAD frequency: 0.00052  dbSNP: rs199798449

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038281	SCV000061950	likely benign	not specified	2011-10-04	criteria provided, single submitter	clinical testing	The Val344Ile variant in MYO6: This variant is not expected to have clinical sig nificance because the Val344 residue is not fully conserved (isoleucine is obser ved in C. elegans) and computational analyses (biochemical amino acid properties , SIFT, AlignGVGD) do not suggest a high likelihood of impact to the protein. Fu rthermore, it was found in a patient with another cause of hearing loss.
Illumina Laboratory Services, Illumina	RCV000329389	SCV000465374	uncertain significance	Autosomal recessive nonsyndromic hearing loss 37	2018-01-12	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	RCV000386285	SCV000465375	uncertain significance	Autosomal dominant nonsyndromic hearing loss 22	2018-01-12	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	RCV001559728	SCV001782019	uncertain significance	not provided	2019-02-07	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae	RCV001559728	SCV002951606	benign	not provided	2023-06-22	criteria provided, single submitter	clinical testing