ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.13423A>G (p.Arg4475Gly)

gnomAD frequency: 0.00006  dbSNP: rs753823008
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001348716 SCV001543026 uncertain significance not provided 2023-10-23 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 4475 of the USH2A protein (p.Arg4475Gly). This variant is present in population databases (rs753823008, gnomAD 0.01%). This missense change has been observed in individual(s) with retinitis pigmentosa (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1044470). 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 not expected to disrupt USH2A protein function with a negative predictive value of 95%. 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.
Ambry Genetics RCV002545595 SCV003654455 uncertain significance Inborn genetic diseases 2022-10-04 criteria provided, single submitter clinical testing The c.13423A>G (p.R4475G) alteration is located in exon 63 (coding exon 62) of the USH2A gene. This alteration results from a A to G substitution at nucleotide position 13423, causing the arginine (R) at amino acid position 4475 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV003449977 SCV004183170 uncertain significance Retinitis pigmentosa 39 2023-11-04 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001825947 SCV004183171 uncertain significance Usher syndrome type 2A 2023-11-04 criteria provided, single submitter clinical testing
Natera, Inc. RCV001825947 SCV002088263 uncertain significance Usher syndrome type 2A 2020-06-18 no assertion criteria provided clinical testing

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