ClinVar Miner

Submissions for variant NM_032578.4(MYPN):c.2857C>T (p.His953Tyr)

gnomAD frequency: 0.00001  dbSNP: rs1042480350
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000696679 SCV000825252 uncertain significance Dilated cardiomyopathy 1KK 2021-02-18 criteria provided, single submitter clinical testing This sequence change replaces histidine with tyrosine at codon 953 of the MYPN protein (p.His953Tyr). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MYPN-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 RCV004026383 SCV005029310 uncertain significance Cardiovascular phenotype 2023-02-13 criteria provided, single submitter clinical testing The p.H953Y variant (also known as c.2857C>T), located in coding exon 12 of the MYPN gene, results from a C to T substitution at nucleotide position 2857. The histidine at codon 953 is replaced by tyrosine, 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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