ClinVar Miner

Submissions for variant NM_020433.5(JPH2):c.424G>T (p.Gly142Ter)

dbSNP: rs765874503
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000579148 SCV000680912 likely pathogenic not provided 2022-07-06 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002330996 SCV002630336 uncertain significance Cardiovascular phenotype 2022-03-09 criteria provided, single submitter clinical testing The p.G142* variant (also known as c.424G>T), located in coding exon 2 of the JPH2 gene, results from a G to T substitution at nucleotide position 424. This changes the amino acid from a glycine to a stop codon within coding exon 2. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Although biallelic loss of function alterations in JPH2 have been associated with autosomal recessive dilated cardiomyopathy, haploinsufficiency for JPH2 has not been clearly established as a mechanism of disease for autosomal dominant hypertrophic cardiomyopathy. Based on the supporting evidence, this variant is expected to be causative of autosomal recessive dilated cardiomyopathy when present along with a second pathogenic variant on the other allele; however, its clinical significance for autosomal dominant hypertrophic cardiomyopathy is unclear.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000579148 SCV004562665 likely pathogenic not provided 2023-10-03 criteria provided, single submitter clinical testing The JPH2 c.424G>T; p.Gly142Ter variant, to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 488956). This variant is only observed on one allele in the Genome Aggregation Database (v2.1.1), indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be likely pathogenic.

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