Submissions for variant NM_006790.3(MYOT):c.1286C>G (p.Ala429Gly)

gnomAD frequency: 0.00012  dbSNP: rs144731446

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000295763	SCV000343219	uncertain significance	not provided	2016-07-12	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000639970	SCV000453019	uncertain significance	Myofibrillar myopathy 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.
Illumina Laboratory Services, Illumina	RCV000335309	SCV000453020	uncertain significance	Myofibrillar Myopathy, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000402251	SCV000453021	uncertain significance	Limb-Girdle Muscular Dystrophy, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Invitae	RCV000639970	SCV000761556	uncertain significance	Myofibrillar myopathy 3	2024-01-17	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 429 of the MYOT protein (p.Ala429Gly). This variant is present in population databases (rs144731446, gnomAD 0.03%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with MYOT-related conditions. ClinVar contains an entry for this variant (Variation ID: 288959). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics	RCV000639970	SCV000897203	uncertain significance	Myofibrillar myopathy 3	2018-10-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000295763	SCV001817641	likely benign	not provided	2019-10-21	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000639970	SCV003810965	likely benign	Myofibrillar myopathy 3	2023-09-25	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003323496	SCV004029021	likely benign	not specified	2023-07-29	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003417907	SCV004115251	uncertain significance	MYOT-related disorder	2023-03-22	criteria provided, single submitter	clinical testing	The MYOT c.1286C>G variant is predicted to result in the amino acid substitution p.Ala429Gly. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.033% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/5-137222648-C-G). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.