Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000600437 | SCV000713321 | uncertain significance | not specified | 2017-06-19 | criteria provided, single submitter | clinical testing | The p.Ala53Val in MYOM1 has not been previously reported in individuals with car diomyopathy, but has been identified in 19/125648 European chromosomes by the Ge nome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs747 035411). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinica l significance of the p.Ala53Val variant is uncertain. |
| Ambry Genetics | RCV000620975 | SCV000739882 | uncertain significance | Cardiovascular phenotype | 2013-08-07 | criteria provided, single submitter | clinical testing | The p.A53V variant (also known as c.158C>T) is located in coding exon 1 of the MYOM1 gene. This alteration results from a C to T substitution at nucleotide position 158. The alanine at codon 53 is replaced by valine, an amino acid with similar properties. This variant was not reported in population-based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), the 1000 Genomes Project and the NHLBI Exome Sequencing Project (ESP). In the ESP, this variant was not observed in 6205 samples (12410 alleles) with coverage at this position. Based on a limited protein sequence alignment, this amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be benign by Polyphen, yet deleterious by SIFT in silico analyses, respectively. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |
| Invitae | RCV000794215 | SCV000933609 | uncertain significance | Hypertrophic cardiomyopathy | 2022-09-14 | criteria provided, single submitter | clinical testing | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 505876). This variant has not been reported in the literature in individuals affected with MYOM1-related conditions. This variant is present in population databases (rs747035411, gnomAD 0.02%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 53 of the MYOM1 protein (p.Ala53Val). |