ClinVar Miner

Submissions for variant NM_032578.4(MYPN):c.3959T>C (p.Leu1320Pro)

gnomAD frequency: 0.00001  dbSNP: rs200646285
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000817505 SCV000958069 uncertain significance Dilated cardiomyopathy 1KK 2023-06-29 criteria provided, single submitter clinical testing 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 660335). This missense change has been observed in individual(s) with left ventricular noncompaction (PMID: 28798025). This variant is present in population databases (rs200646285, gnomAD 0.0009%). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1320 of the MYPN protein (p.Leu1320Pro).
GeneDx RCV001759591 SCV001985750 uncertain significance not provided 2024-10-23 criteria provided, single submitter clinical testing Reported in a patient with left ventricular noncompaction who also harbored additional cardiogenetic variants (PMID: 28798025); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28798025)
Ambry Genetics RCV002352439 SCV002621062 uncertain significance Cardiovascular phenotype 2024-11-14 criteria provided, single submitter clinical testing The p.L1320P variant (also known as c.3959T>C), located in coding exon 19 of the MYPN gene, results from a T to C substitution at nucleotide position 3959. The leucine at codon 1320 is replaced by proline, an amino acid with similar properties. This variant was reported in individuals in cardiomyopathy cohorts; however, clinical details were limited and additional alterations in other cardiac-related genes were identified (Miszalski-Jamka K et al. Circ Cardiovasc Genet, 2017 Aug;10:[ePub ahead of print]; Koutsofti C et al. Genes (Basel), 2024 Feb;15:[ePub ahead of print]). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.

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