Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000667613 | SCV000792091 | uncertain significance | Usher syndrome type 2A; Retinitis pigmentosa 39 | 2017-06-08 | criteria provided, single submitter | clinical testing | |
Cytogenetics and Genomics Laboratory, |
RCV000754979 | SCV000803389 | uncertain significance | Leber congenital amaurosis | 2018-06-01 | criteria provided, single submitter | research | |
Labcorp Genetics |
RCV001246671 | SCV001420046 | uncertain significance | not provided | 2022-06-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 2354 of the USH2A protein (p.Arg2354His). This variant is present in population databases (rs201386640, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of Usher syndrome (PMID: 17085681). ClinVar contains an entry for this variant (Variation ID: 552369). 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 histidine 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001805789 | SCV002050829 | uncertain significance | not specified | 2021-12-08 | criteria provided, single submitter | clinical testing | Variant summary: USH2A c.7061G>A (p.Arg2354His) results in a conservative amino acid change located in the Fibronectin type III domain (IPR003961) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6.4e-05 in 251280 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in USH2A causing Usher Syndrome (6.4e-05 vs 0.011), allowing no conclusion about variant significance. c.7061G>A has been reported in the literature in individuals affected with Usher Syndrome and other conditions with vision and hearing loss (example: Aller_2006, Glen_2019), but these data do not allow any conclusion about variant significance. Co-occurrences with other pathogenic variants have been reported (RPE65 c.1338G>T, p.Arg446Ser), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters have assessed this variant since 2014, where all submitters have classified the variant as of uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Genome- |
RCV003451660 | SCV004181565 | uncertain significance | Retinitis pigmentosa 39 | 2023-11-04 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV001835082 | SCV004181566 | uncertain significance | Usher syndrome type 2A | 2023-11-04 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV003451660 | SCV004208138 | uncertain significance | Retinitis pigmentosa 39 | 2023-11-07 | criteria provided, single submitter | clinical testing | |
Breakthrough Genomics, |
RCV001246671 | SCV005187238 | uncertain significance | not provided | criteria provided, single submitter | not provided | ||
Gene |
RCV001246671 | SCV005401152 | uncertain significance | not provided | 2024-05-16 | criteria provided, single submitter | clinical testing | In silico analysis indicates that this missense variant does not alter protein structure/function; Identified in a patient with hearing loss, night blindness, and reduced vision who as also heterozygous, phase unknown, for two lpath/path variants in the USH2A gene in published literature (PMID: 17085681); Identified in a patient with Leber congenital amaurosis who is homozygous for a variant in the RPE65 gene and heterozygous for a second variant in the USH2A gene (phase unknown) in published literature (PMID: 30870047); This variant is associated with the following publications: (PMID: 17085681, 30870047) |
Natera, |
RCV001835082 | SCV002090864 | uncertain significance | Usher syndrome type 2A | 2020-01-11 | no assertion criteria provided | clinical testing |