Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
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, |
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. |