ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.15281C>T (p.Pro5094Leu) (rs727503714)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000152563 SCV000201800 uncertain significance not specified 2014-06-10 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Pro5094Leu vari ant in USH2A has not been previously reported in individuals with hearing loss a nd was absent from large population studies. The proline (Pro) at position 5094 is not conserved in mammals or evolutionary distant species, suggesting that var iation at this position may be tolerated. Other computational prediction tools d o not provide strong support for or against an impact to the protein. In summary , the clinical significance of this variant cannot be determined with certainty; however, based upon conservation data, we would lean towards a more likely beni gn role.
Counsyl RCV000666221 SCV000790478 uncertain significance Usher syndrome, type 2A; Retinitis pigmentosa 39 2017-04-04 criteria provided, single submitter clinical testing
Invitae RCV001239388 SCV001412261 uncertain significance not provided 2019-10-13 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 5094 of the USH2A protein (p.Pro5094Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs727503714, ExAC 0.004%). This variant has not been reported in the literature in individuals with USH2A-related disease. ClinVar contains an entry for this variant (Variation ID: 166415). 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: "Benign"; 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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