Submissions for variant NM_020366.4(RPGRIP1):c.2063C>T (p.Ser688Leu)

gnomAD frequency: 0.00011  dbSNP: rs543867152

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001113174	SCV001270927	uncertain significance	Cone-rod dystrophy 13	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.
Illumina Laboratory Services, Illumina	RCV001113175	SCV001270928	uncertain significance	Leber congenital amaurosis 6	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001245884	SCV001419206	uncertain significance	Cone-rod dystrophy 13; Leber congenital amaurosis 6	2022-10-24	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 688 of the RPGRIP1 protein (p.Ser688Leu). This variant is present in population databases (rs543867152, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with RPGRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 883035). 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 RPGRIP1 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.
Genome-Nilou Lab	RCV001113175	SCV002045011	uncertain significance	Leber congenital amaurosis 6	2021-11-07	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001113174	SCV002045022	uncertain significance	Cone-rod dystrophy 13	2021-11-07	criteria provided, single submitter	clinical testing