Submissions for variant NM_000322.5(PRPH2):c.811del (p.Leu271fs)

dbSNP: rs1582764528

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002536891	SCV003484021	pathogenic	PRPH2-related disorder	2022-06-11	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu271Serfs*7) in the PRPH2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 76 amino acid(s) of the PRPH2 protein. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the PRPH2 protein in which other variant(s) (p.Val332Glu) have been determined to be pathogenic (PMID: 32531846; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 636077). This premature translational stop signal has been observed in individual(s) with autosomal dominant macular dystrophy (PMID: 30718709). This variant is not present in population databases (gnomAD no frequency).
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet	RCV000787670	SCV000926660	likely pathogenic	Macular dystrophy	2018-04-01	no assertion criteria provided	research
Leiden Open Variation Database	RCV001530256	SCV001745004	pathogenic	not provided	2021-04-06	no assertion criteria provided	curation	Curator: Global Variome, with Curator vacancy. Submitter to LOVD: Manon Peeters.