ClinVar Miner

Submissions for variant NM_032578.4(MYPN):c.2051C>G (p.Ser684Cys)

gnomAD frequency: 0.00001  dbSNP: rs577089308
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV006666625 SCV007555091 uncertain significance Cardiovascular phenotype 2026-02-09 criteria provided, single submitter clinical testing The p.S684C variant (also known as c.2051C>G), located in coding exon 10 of the MYPN gene, results from a C to G substitution at nucleotide position 2051. The serine at codon 684 is replaced by cysteine, an amino acid with dissimilar properties. This variant was reported in individual(s) with features consistent with dilated cardiomyopathy (DCM) (Mazzarotto F et al. Circulation, 2020 Feb;141:387-398). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
Baylor Genetics RCV001045264 SCV004040927 uncertain significance Dilated cardiomyopathy 1KK 2023-01-09 criteria provided, single submitter clinical testing
Baylor Genetics RCV003333122 SCV004040650 uncertain significance MYPN-related myopathy 2023-01-09 criteria provided, single submitter clinical testing
GeneDx RCV003160335 SCV003915287 uncertain significance not provided 2022-10-04 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31983221)
Labcorp Genetics (formerly Invitae), Labcorp RCV001045264 SCV001209104 uncertain significance Dilated cardiomyopathy 1KK 2022-04-17 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 684 of the MYPN protein (p.Ser684Cys). This variant is present in population databases (rs577089308, gnomAD 0.02%). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 31983221). ClinVar contains an entry for this variant (Variation ID: 842785). 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: "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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