Submissions for variant NM_001029883.3(PCARE):c.403G>A (p.Glu135Lys)

gnomAD frequency: 0.00028  dbSNP: rs200227182

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001141643	SCV001302004	uncertain significance	Retinitis pigmentosa	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Invitae	RCV001210785	SCV001382291	uncertain significance	not provided	2022-10-18	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 135 of the PCARE protein (p.Glu135Lys). This variant is present in population databases (rs200227182, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with PCARE-related conditions. ClinVar contains an entry for this variant (Variation ID: 898032). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
CeGaT Center for Human Genetics Tuebingen	RCV001210785	SCV004701398	uncertain significance	not provided	2024-02-01	criteria provided, single submitter	clinical testing	PCARE: PM2, BP4
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001210785	SCV001963235	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001210785	SCV001973379	uncertain significance	not provided		no assertion criteria provided	clinical testing