ClinVar Miner

Submissions for variant NM_000322.5(PRPH2):c.389T>C (p.Leu130Pro)

dbSNP: rs1761911206
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001212513 SCV001384098 pathogenic PRPH2-related disorder 2024-11-04 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 130 of the PRPH2 protein (p.Leu130Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant retinitis pigmentosa (PMID: 22842402, 23950152, 28559085; internal data). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 942510). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt PRPH2 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
NEI Ophthalmic Genomics Laboratory, National Institutes of Health RCV001250303 SCV001424616 likely pathogenic Retinitis pigmentosa 2020-01-07 criteria provided, single submitter clinical testing The variant NM_000322.4:c.389T>C in the PRPH2 gene has been previously studied (PMIDs 22842402, 28559085). We found this variant in 4 patient(s) in a PRPH2 cohort study (Reeves et al. 2020). This variant is listed in dbSNP and/or HGMD (CM127034). It is absent in gnomAD browser. It is enriched in the PRPH2 disease cohort. We invoked ACMG criteria [PS4, PM2, PP3, PP1] and classified NM_000322.4:c.389T>C in the PRPH2 gene as a Likely Pathogenic mutation.
GeneDx RCV001530282 SCV001767266 likely pathogenic not provided 2024-10-18 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); 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: 22842402, 28559085, 23950152, 32531846, 34411390)
Leiden Open Variation Database RCV001530282 SCV001745040 likely pathogenic not provided 2021-04-06 no assertion criteria provided curation Curator: Global Variome, with Curator vacancy. Submitters to LOVD: LOVD, Manon Peeters.

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