ClinVar Miner

Submissions for variant NM_000322.5(PRPH2):c.494G>T (p.Cys165Phe)

dbSNP: rs61755788
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
NEI Ophthalmic Genomics Laboratory, National Institutes of Health RCV001250330 SCV001424650 uncertain significance Retinitis pigmentosa 2020-01-07 criteria provided, single submitter clinical testing The variant NM_000322.4:c.494G>T in the PRPH2 gene has been previously studied(PMID Souied et al. (1995), & 9673478). We found this variant in 1 patient(s) in a PRPH2 cohort study (Reeves et al. 2020). This variant is listed in dbSNP and/or HGMD (CM951118). It is absent in gnomAD browser. It is not enriched in the PRPH2 disease cohort. We invoked ACMG criteria [PM1, PM2, PP3] and classified NM_000322.4:c.494G>T in the PRPH2 gene as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001379008 SCV001576722 pathogenic PRPH2-related disorder 2022-10-17 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Cys165 amino acid residue in PRPH2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9673478, 10747861, 25447119). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 165 of the PRPH2 protein (p.Cys165Phe). 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. ClinVar contains an entry for this variant (Variation ID: 973717). This missense change has been observed in individuals with clinical features of PRPH2-related conditions (PMID: 32531846; Invitae). This variant is not present in population databases (gnomAD no frequency).
Leiden Open Variation Database RCV001530224 SCV001744951 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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