ClinVar Miner

Submissions for variant NM_206933.3(USH2A):c.14419G>A (p.Ala4807Thr) (rs534656527)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Hearing Loss Variant Curation Expert Panel RCV000710342 SCV000840539 uncertain significance Usher syndrome 2018-09-28 reviewed by expert panel curation The c.14419G>A (p.Ala4807Thr) variant in USH2A has been observed in at least one individual with hearing loss (Partners LMM ClinVar SCV000272892.2; PS4 not met). The variant has been observed in 0.01% (5/30782) of South Asian chromosomes by the Genome Aggregation Database (, which is a low enough frequency to award PM2_Supporting based on the thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss (PM2_Supporting). In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: PM2_Supporting.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724765 SCV000231954 uncertain significance not provided 2015-04-28 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000215244 SCV000272892 uncertain significance not specified 2015-03-25 criteria provided, single submitter clinical testing The p.Ala4807Thr variant in USH2A has not been previously reported in individual s with hearing loss, but has been identified in 5/66724 European chromosomes and 5/16512 South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http ://; dbSNP rs534656527). Computational prediction tools a nd conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Ala4807Thr varian t is uncertain.
Counsyl RCV000665441 SCV000789566 uncertain significance Usher syndrome, type 2A; Retinitis pigmentosa 39 2017-02-14 criteria provided, single submitter clinical testing
Invitae RCV000724765 SCV001216666 uncertain significance not provided 2019-11-07 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 4807 of the USH2A protein (p.Ala4807Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs534656527, ExAC 0.03%). This variant has not been reported in the literature in individuals with USH2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 198366). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.

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