ClinVar Miner

Submissions for variant NM_032578.4(MYPN):c.3763G>A (p.Val1255Met)

gnomAD frequency: 0.00006  dbSNP: rs750655311
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Total submissions: 5
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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 RCV000222515 SCV000272187 uncertain significance not specified 2016-03-18 criteria provided, single submitter clinical testing The p.Val1255Met variant in MYPN has not been previously reported in individuals with cardiomyopathy, but has been identified in 2/11564 of Latino chromosomes b y the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs750655311). Computational prediction tools and conservation analysis do not pr ovide strong support for or against an impact to the protein. In summary, the cl inical significance of the p.Val1255Met variant is uncertain.
Invitae RCV000463619 SCV000553461 uncertain significance Dilated cardiomyopathy 1KK 2022-08-16 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1255 of the MYPN protein (p.Val1255Met). This variant is present in population databases (rs750655311, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with MYPN-related conditions. ClinVar contains an entry for this variant (Variation ID: 229036). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV001256744 SCV001433151 uncertain significance Dilated cardiomyopathy 1A 2019-03-15 criteria provided, single submitter clinical testing
GeneDx RCV002272178 SCV002558069 uncertain significance not provided 2022-07-15 criteria provided, single submitter clinical testing Reported in one Spanish patient with DCM (Pea-Pea et al., 2021); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 32826072)
Ambry Genetics RCV002347845 SCV002623379 uncertain significance Cardiovascular phenotype 2018-06-01 criteria provided, single submitter clinical testing The p.V1255M variant (also known as c.3763G>A), located in coding exon 18 of the MYPN gene, results from a G to A substitution at nucleotide position 3763. The valine at codon 1255 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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