Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000216488 | SCV000272174 | uncertain significance | not specified | 2016-01-29 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The p.Met1453Leu va riant in MYOM1 has not been previously reported in individuals with cardiomyopat hy, but has been identified in 5/19248 European chromosomes by the Exome Aggrega tion Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs181642354). Methi onine (Met) at position 1453 is not conserved in mammals or evolutionarily dista nt species, raising the possibility that a change at this position may be tolera ted. In summary, while the clinical significance of the p.Met1453Leu variant is uncertain, these data suggest that it is more likely to be benign. |
Labcorp Genetics |
RCV000804278 | SCV000944180 | uncertain significance | Hypertrophic cardiomyopathy | 2024-06-26 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1453 of the MYOM1 protein (p.Met1453Leu). This variant is present in population databases (rs181642354, gnomAD 0.02%). 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: 229026). 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) performed at Invitae indicates that this missense variant is not expected to disrupt MYOM1 protein function with a negative predictive value of 80%. 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 | RCV000216488 | SCV005146093 | uncertain significance | not specified | 2024-05-13 | criteria provided, single submitter | clinical testing | The c.4357A>T (p.M1453L) alteration is located in exon 32 (coding exon 31) of the MYOM1 gene. This alteration results from a A to T substitution at nucleotide position 4357, causing the methionine (M) at amino acid position 1453 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |