ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.5255T>G (p.Leu1752Trp) (rs1469348824)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001002428 SCV001160365 uncertain significance not specified 2019-03-18 criteria provided, single submitter clinical testing The USH2A c.5255T>G; p.Leu1752Trp variant (rs1469348824), to our knowledge, is not reported in the medical literature or gene-specific databases. This variant is also absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The amino acid at this position is moderately conserved and computational algorithms (PolyPhen-2, SIFT) predict this variant is deleterious. Due to limited information, the clinical significance of this variant is uncertain at this time.
Invitae RCV001350169 SCV001544551 uncertain significance not provided 2020-02-08 criteria provided, single submitter clinical testing This sequence change replaces leucine with tryptophan at codon 1752 of the USH2A protein (p.Leu1752Trp). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with USH2A-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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