ClinVar Miner

Submissions for variant NM_170665.4(ATP2A2):c.1805C>T (p.Pro602Leu)

dbSNP: rs121912737
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001650836 SCV001871119 pathogenic not provided 2021-07-30 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect: undetectable ATPase activity and impaired Ca2+ binding and transport (Dhitavat et al., 2003; Dode et al., 2003); Not observed at significant frequency in large population cohorts (Lek et al., 2016); Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); 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: 12975374, 22814319, 28035777, 28498512, 25622760, 12542527, 16716163)
Labcorp Genetics (formerly Invitae), Labcorp RCV001650836 SCV004296225 pathogenic not provided 2023-06-09 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 602 of the ATP2A2 protein (p.Pro602Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with acrokeratosis verruciformis of Hopf (PMID: 12542527, 22814319, 25622760, 28035777, 28498512). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 17799). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ATP2A2 protein function. Experimental studies have shown that this missense change affects ATP2A2 function (PMID: 12542527). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000019377 SCV000039667 pathogenic Acrokeratosis verruciformis of Hopf 2003-02-01 no assertion criteria provided literature only

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