ClinVar Miner

Submissions for variant NM_032578.4(MYPN):c.1096T>C (p.Ser366Pro)

gnomAD frequency: 0.00003  dbSNP: rs535795936
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Revvity Omics, Revvity RCV003133560 SCV003810991 uncertain significance not provided 2020-10-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV002442519 SCV002733684 uncertain significance Cardiovascular phenotype 2025-04-09 criteria provided, single submitter clinical testing The p.S366P variant (also known as c.1096T>C), located in coding exon 3 of the MYPN gene, results from a T to C substitution at nucleotide position 1096. The serine at codon 366 is replaced by proline, an amino acid with similar properties. This alteration has been reported in a dilated cardiomyopathy (DCM) cohort; however, clinical details were limited (Mazzarotto F et al. Circulation, 2020 02;141:387-398). This amino acid position is highly 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000703192 SCV000832080 uncertain significance Dilated cardiomyopathy 1KK 2022-07-08 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 366 of the MYPN protein (p.Ser366Pro). This variant is present in population databases (rs535795936, gnomAD 0.01%). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 31983221). ClinVar contains an entry for this variant (Variation ID: 579816). 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: "Tolerated"; PolyPhen-2: "Possibly 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.

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