ClinVar Miner

Submissions for variant NM_020433.5(JPH2):c.1141C>T (p.Arg381Cys)

gnomAD frequency: 0.00001  dbSNP: rs768172413
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetics and Genomics Program, Sidra Medicine RCV001293109 SCV001434099 uncertain significance Hypertrophic cardiomyopathy criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV001293109 SCV001538967 uncertain significance Hypertrophic cardiomyopathy 2020-05-12 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. 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: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with JPH2-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces arginine with cysteine at codon 381 of the JPH2 protein (p.Arg381Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine.
Ambry Genetics RCV004035375 SCV003589577 uncertain significance Cardiovascular phenotype 2021-11-09 criteria provided, single submitter clinical testing The c.1141C>T (p.R381C) alteration is located in exon 2 (coding exon 2) of the JPH2 gene. This alteration results from a C to T substitution at nucleotide position 1141, causing the arginine (R) at amino acid position 381 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV004762027 SCV005370775 uncertain significance not provided 2023-07-25 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; 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

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