Submissions for variant NM_001029883.3(PCARE):c.1297C>T (p.Pro433Ser)

gnomAD frequency: 0.00044  dbSNP: rs200696965

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000355654	SCV000429886	uncertain significance	Retinitis pigmentosa	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV000766629	SCV000576664	uncertain significance	not provided	2017-04-24	criteria provided, single submitter	clinical testing	The P433S variant in the C2orf71 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The P433S variant is observed in 80/66,738 alleles (0.1%) from individuals of non-Finnish European background in the ExAC dataset, including two homozygous controls (Lek et al., 2016). The P433S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved across species, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret P433S as a variant of uncertain significance.
Eurofins Ntd Llc (ga)	RCV000489456	SCV000860238	likely benign	not specified	2018-03-27	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000765664	SCV000896998	uncertain significance	Retinitis pigmentosa 54	2018-10-31	criteria provided, single submitter	clinical testing
Invitae	RCV000766629	SCV001110218	likely benign	not provided	2024-01-04	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000489456	SCV001160584	likely benign	not specified	2019-06-05	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000766629	SCV002544016	benign	not provided	2024-03-01	criteria provided, single submitter	clinical testing	PCARE: BS1, BS2
PreventionGenetics, part of Exact Sciences	RCV003922450	SCV004739240	benign	PCARE-related condition	2020-12-21	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).