Total submissions: 12
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000414238 | SCV000337866 | uncertain significance | not provided | 2015-12-11 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000414238 | SCV000490476 | likely pathogenic | not provided | 2022-12-07 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25743179, 23304067, 21310491, 15521980, 19753315, 29545425, 31963381, 29331482) |
Counsyl | RCV000004649 | SCV000800518 | uncertain significance | Usher syndrome type 3 | 2017-04-19 | criteria provided, single submitter | clinical testing | |
Centre for Genomic Medicine, |
RCV000004649 | SCV001156372 | pathogenic | Usher syndrome type 3 | 2019-02-01 | criteria provided, single submitter | clinical testing | |
Blueprint Genetics | RCV001075346 | SCV001240966 | uncertain significance | Retinal dystrophy | 2018-04-11 | criteria provided, single submitter | clinical testing | |
Institute of Medical Genetics and Applied Genomics, |
RCV000414238 | SCV001905531 | likely pathogenic | not provided | 2021-09-15 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000414238 | SCV002163401 | pathogenic | not provided | 2022-10-31 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 40 of the CLRN1 protein (p.Cys40Gly). This variant is present in population databases (rs121908143, gnomAD 0.01%). This missense change has been observed in individual(s) with Usher syndrome (PMID: 15521980; Invitae). ClinVar contains an entry for this variant (Variation ID: 4399). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002468960 | SCV002766549 | likely pathogenic | Usher syndrome | 2022-11-14 | criteria provided, single submitter | clinical testing | Variant summary: CLRN1 c.118T>G (p.Cys40Gly) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-05 in 251462 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in CLRN1 causing Usher Syndrome (8e-05 vs 0.0014), allowing no conclusion about variant significance. c.118T>G has been reported in the literature as biallelic homozygous or compound heterozygous genotypes in individuals affected with features of Usher Syndrome type 3 and as a heterozygous genotype in one case report with Unilateral retinitis pigmentosa (RP) (example, Aller_2004, Haer-Wigman_2017, Yong Sim_2018, Whelan_2020, Jiman_2020). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Nine clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (LP/P, n=4; VUS, n=5). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
Baylor Genetics | RCV003466815 | SCV004214403 | likely pathogenic | Retinitis pigmentosa 61 | 2023-10-14 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000004649 | SCV000024823 | pathogenic | Usher syndrome type 3 | 2004-12-01 | no assertion criteria provided | literature only | |
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000004649 | SCV000804616 | uncertain significance | Usher syndrome type 3 | 2016-09-01 | no assertion criteria provided | clinical testing | |
Natera, |
RCV001273484 | SCV001456566 | likely pathogenic | Usher syndrome type 3A | 2020-09-16 | no assertion criteria provided | clinical testing |