Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Blueprint Genetics | RCV001075873 | SCV001241514 | likely pathogenic | Retinal dystrophy | 2019-08-14 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001204623 | SCV001375836 | uncertain significance | not provided | 2021-08-13 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with histidine at codon 2279 of the USH2A protein (p.Asp2279His). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and histidine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with clinical features of USH2A-related conditions (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65". 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, |
RCV002469344 | SCV002766558 | uncertain significance | not specified | 2022-11-21 | criteria provided, single submitter | clinical testing | Variant summary: USH2A c.6835G>C (p.Asp2279His) results in a non-conservative amino acid change located in the Fibronectin type III domain (IPR003961) of the encoded protein sequence. Three of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250976 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.6835G>C has been reported in the literature in individuals affected with Usher syndrome or nonsyndromic autosomal recessive retinitis pigmentosa (Hufnagel__2022). The report does not provide unequivocal conclusions about association of the variant with Usher Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. ClinVar submitters (evaluation after 2014) cite this variant as uncertain significance and likely pathogenic. Based on the evidence outlined above, the variant was classified as uncertain significance. |