ClinVar Miner

Submissions for variant NM_003803.4(MYOM1):c.3125C>T (p.Pro1042Leu)

gnomAD frequency: 0.00004  dbSNP: rs761951856
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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 RCV000215987 SCV000272168 uncertain significance not specified 2015-11-09 criteria provided, single submitter clinical testing The p.Pro1042Leu variant in MYOM1 has not been previously reported in individual s with cardiomyopathy, but has been identified in 3/63706 European chromosomes b y the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs761951856). Computational prediction tools and conservation analysis suggest t hat the p.Pro1042Leu variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical signi ficance of the p.Pro1042Leu variant is uncertain.
Invitae RCV000812282 SCV000952591 uncertain significance Hypertrophic cardiomyopathy 2023-12-11 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1042 of the MYOM1 protein (p.Pro1042Leu). This variant is present in population databases (rs761951856, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with MYOM1-related conditions. ClinVar contains an entry for this variant (Variation ID: 229020). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MYOM1 protein function. 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.
Ambry Genetics RCV003372657 SCV004097216 uncertain significance Inborn genetic diseases 2023-06-17 criteria provided, single submitter clinical testing The p.P1042L variant (also known as c.3125C>T), located in coding exon 20 of the MYOM1 gene, results from a C to T substitution at nucleotide position 3125. The proline at codon 1042 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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