ClinVar Miner

Submissions for variant NM_003803.4(MYOM1):c.3278C>T (p.Ala1093Val)

gnomAD frequency: 0.00005  dbSNP: rs749676865
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000218960 SCV000272169 uncertain significance not specified 2015-11-12 criteria provided, single submitter clinical testing The p.Ala1093Val variant in MYOM1 has not been previously reported in individual s with cardiomyopathy, but has been identified in 3/58954 European chromosomes b y the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs749676865). Alanine (Ala) at position 1093 is not conserved in mammals or evol utionarily distant species and 2 mammals (black flying fox, megabat) carry a val ine (Val) at this position, raising the possibility that this change may be tole rated. In summary, the clinical significance of the p.Ala1093Val variant is unce rtain.
Invitae RCV001322796 SCV001513684 uncertain significance Hypertrophic cardiomyopathy 2022-04-09 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1093 of the MYOM1 protein (p.Ala1093Val). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 229021). This variant has not been reported in the literature in individuals affected with MYOM1-related conditions. This variant is present in population databases (rs749676865, gnomAD 0.004%).
Ambry Genetics RCV002321841 SCV002606493 uncertain significance Inborn genetic diseases 2021-11-19 criteria provided, single submitter clinical testing The p.A1093V variant (also known as c.3278C>T), located in coding exon 20 of the MYOM1 gene, results from a C to T substitution at nucleotide position 3278. The alanine at codon 1093 is replaced by valine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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