ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.12958G>C (p.Asp4320His)

gnomAD frequency: 0.00001  dbSNP: rs140202956
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001066962 SCV001231988 pathogenic not provided 2024-06-26 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 4320 of the USH2A protein (p.Asp4320His). This variant is present in population databases (rs140202956, gnomAD 0.02%). This missense change has been observed in individuals with clinical features of Usher syndrome and inherited retinal dystrophy (Invitae). ClinVar contains an entry for this variant (Variation ID: 860622). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on USH2A protein function. This variant disrupts the p.Asp4320 amino acid residue in USH2A. Other variant(s) that disrupt this residue have been observed in individuals with USH2A-related conditions (Invitae), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences RCV004536129 SCV004118042 uncertain significance USH2A-related disorder 2023-07-18 criteria provided, single submitter clinical testing The USH2A c.12958G>C variant is predicted to result in the amino acid substitution p.Asp4320His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0080% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-215848295-C-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Natera, Inc. RCV001827433 SCV002088285 uncertain significance Usher syndrome type 2A 2021-01-13 no assertion criteria provided clinical testing

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