Submissions for variant NM_000322.5(PRPH2):c.995T>A (p.Val332Glu)

dbSNP: rs1582759492

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001248001	SCV001421460	likely pathogenic	PRPH2-related disorder	2022-08-10	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) performed at Invitae indicates that this missense variant is expected to disrupt PRPH2 protein function. ClinVar contains an entry for this variant (Variation ID: 636192). This missense change has been observed in individuals with clinical features of autosomal dominant PRPH2-related conditions (PMID: 30718709, 32531846; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 332 of the PRPH2 protein (p.Val332Glu).
NEI Ophthalmic Genomics Laboratory, National Institutes of Health	RCV001250383	SCV001424719	uncertain significance	Cone-rod dystrophy	2020-01-07	criteria provided, single submitter	clinical testing	The variant NM_000322.4:c.995T>A in the PRPH2 gene has been previously studied(PMID 30718709). 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 (CM192683). It is absent in gnomAD browser. It is not enriched in the PRPH2 disease cohort. We invoked ACMG criteria [PM2, PP3] and classified NM_000322.4:c.995T>A in the PRPH2 gene as a Variant of Uncertain Significance.
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet	RCV000787868	SCV000926884	uncertain significance	Macular dystrophy	2018-04-01	no assertion criteria provided	research
Leiden Open Variation Database	RCV001530393	SCV001745206	uncertain significance	not provided	2021-04-06	no assertion criteria provided	curation	Curator: Global Variome, with Curator vacancy. Submitter to LOVD: Manon Peeters.