ClinVar Miner

Submissions for variant NM_020433.5(JPH2):c.458T>C (p.Val153Ala)

gnomAD frequency: 0.00001  dbSNP: rs776045429
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000767063 SCV000235926 uncertain significance not provided 2014-03-11 criteria provided, single submitter clinical testing The V153A variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The V153A variant was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Nevertheless, the V153A variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved across species. In silico analysis predicts this variant likely does not alter the protein structure/function. No missense mutations in nearby residues have been reported in association with cardiomyopathy, indicating this region of the protein may be tolerant of change. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. This variant is found in the CARDIOMYOPATHY panel(s).
Fulgent Genetics, Fulgent Genetics RCV000764238 SCV000895241 uncertain significance Hypertrophic cardiomyopathy 17 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000819506 SCV000960170 uncertain significance Hypertrophic cardiomyopathy 2023-12-13 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 153 of the JPH2 protein (p.Val153Ala). This variant is present in population databases (rs776045429, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with JPH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 201795). 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 tolerated. 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.
Ambry Genetics RCV004020216 SCV005027908 likely benign Cardiovascular phenotype 2023-11-13 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000183466 SCV000280103 uncertain significance not specified 2014-03-18 no assertion criteria provided clinical testing Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease

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