ClinVar Miner

Submissions for variant NM_000322.5(PRPH2):c.683C>T (p.Thr228Ile)

gnomAD frequency: 0.00001  dbSNP: rs369507460
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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 RCV001051591 SCV001215756 likely pathogenic PRPH2-related disorder 2023-08-03 criteria provided, single submitter clinical testing 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PRPH2 protein function. ClinVar contains an entry for this variant (Variation ID: 847943). This missense change has been observed in individual(s) with autosomal dominant pattern dystrophy (PMID: 25082885, 32531846). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs369507460, gnomAD 0.009%). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 228 of the PRPH2 protein (p.Thr228Ile).
NEI Ophthalmic Genomics Laboratory, National Institutes of Health RCV001250315 SCV001424635 likely pathogenic Patterned dystrophy of the retinal pigment epithelium 2020-01-07 criteria provided, single submitter clinical testing The variant NM_000322.4:c.683C>T in the PRPH2 gene has been previously studied(PMID 25082885). 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 (rs369507460). It is present in gnomAD browser (AF 0.0000406). This variant is not already listed in ClinVar. It is not enriched in the PRPH2 disease cohort. We invoked ACMG criteria [PM1, PM2, PP1, PP3] and classified NM_000322.4:c.683C>T in the PRPH2 gene as a Likely Pathogenic mutation.
NEI Ophthalmic Genomics Laboratory, National Institutes of Health RCV001250332 SCV001424652 likely pathogenic Stargardt disease 2020-01-07 criteria provided, single submitter clinical testing The variant NM_000322.4:c.683C>T in the PRPH2 gene has been previously studied(PMID 25082885). 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 (rs369507460). It is present in gnomAD browser (AF 0.0000406). This variant is not already listed in ClinVar. It is not enriched in the PRPH2 disease cohort. We invoked ACMG criteria [PM1, PM2, PP1, PP3] and classified NM_000322.4:c.683C>T in the PRPH2 gene as a Likely Pathogenic mutation.
Leiden Open Variation Database RCV001530252 SCV001744998 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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