ClinVar Miner

Submissions for variant NM_000322.5(PRPH2):c.665G>C (p.Cys222Ser)

dbSNP: rs1442844778
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV001075398 SCV001241020 likely pathogenic Retinal dystrophy 2018-07-19 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001386138 SCV001586267 pathogenic PRPH2-related disorder 2021-08-02 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Cys222 amino acid residue in PRPH2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 28559085, 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. This missense change has been observed in individual(s) with autosomal dominant retinitis pigmentosa or macular dystrophy (PMID: 25447119, 25390130). ClinVar contains an entry for this variant (Variation ID: 866971). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with serine at codon 222 of the PRPH2 protein (p.Cys222Ser). The cysteine residue is highly conserved and there is a moderate physicochemical difference between cysteine and serine.
GeneDx RCV001530248 SCV003842650 uncertain significance not provided 2022-09-13 criteria provided, single submitter clinical testing Published functional studies suggest this variant may result in impairment of protein folding, however additional studies are needed to validate the functional effect of this variant (Goldberg et al., 1998); 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: 34411390, 25390130, 17296903, 25447119, 9425091, 33090715)
Leiden Open Variation Database RCV001530248 SCV001744994 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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