ClinVar Miner

Submissions for variant NM_000322.5(PRPH2):c.457A>G (p.Lys153Glu)

dbSNP: rs2152010930
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001530340 SCV002007280 uncertain significance not provided 2019-05-28 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 25910913)
Labcorp Genetics (formerly Invitae), Labcorp RCV001873758 SCV002274282 likely pathogenic PRPH2-related disorder 2022-10-05 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with autosomal dominant PRPH2-related conditions (PMID: 25910913; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 153 of the PRPH2 protein (p.Lys153Glu). ClinVar contains an entry for this variant (Variation ID: 1175280). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Lys153 amino acid residue in PRPH2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8994365, 19038374; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 expected to disrupt PRPH2 protein function.
Leiden Open Variation Database RCV001530340 SCV001745135 likely pathogenic not provided 2021-04-06 no assertion criteria provided curation Curator: Global Variome, with Curator vacancy. Submitter to LOVD: Manon Peeters.

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