ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.14350G>A (p.Glu4784Lys)

gnomAD frequency: 0.00003  dbSNP: rs746837034
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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 RCV001240871 SCV001413849 pathogenic not provided 2023-10-23 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 4784 of the USH2A protein (p.Glu4784Lys). This variant is present in population databases (rs746837034, gnomAD 0.006%). This missense change has been observed in individual(s) with retinitis pigmentosa and/or Usher syndrome (PMID: 31456290, 32675063, 33124170; 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: 812447). 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. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001240871 SCV001987324 uncertain significance not provided 2018-10-22 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31456290, 33124170)
Baylor Genetics RCV003461305 SCV004208343 likely pathogenic Retinitis pigmentosa 39 2024-03-10 criteria provided, single submitter clinical testing
Sharon lab, Hadassah-Hebrew University Medical Center RCV001003252 SCV001161332 likely pathogenic Retinitis pigmentosa 2019-06-23 no assertion criteria provided research
Natera, Inc. RCV001836060 SCV002088226 uncertain significance Usher syndrome type 2A 2020-08-08 no assertion criteria provided clinical testing

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