ClinVar Miner

Submissions for variant NM_032578.4(MYPN):c.1081G>T (p.Val361Phe)

gnomAD frequency: 0.00001  dbSNP: rs527628617
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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 RCV001928597 SCV002179570 uncertain significance Dilated cardiomyopathy 1KK 2022-07-19 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 361 of the MYPN protein (p.Val361Phe). 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: 1414251). This missense change has been observed in individual(s) with clinical features of MYPN-related conditions (PMID: 30847666). This variant is present in population databases (rs527628617, gnomAD 0.006%).
Ambry Genetics RCV002425238 SCV002729287 uncertain significance Cardiovascular phenotype 2022-09-07 criteria provided, single submitter clinical testing The p.V361F variant (also known as c.1081G>T), located in coding exon 3 of the MYPN gene, results from a G to T substitution at nucleotide position 1081. The valine at codon 361 is replaced by phenylalanine, an amino acid with highly similar properties. This variant was detected in a cardiomyopathy/arrhythmia genetic testing cohort; however, clinical details were limited (van Lint FHM et al. Neth Heart J, 2019 Jun;27:304-309). This amino acid position is not well conserved in available vertebrate species. 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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