ClinVar Miner

Submissions for variant NM_206933.3(USH2A):c.9433C>T (p.Leu3145Phe)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Hearing Loss Variant Curation Expert Panel RCV001252675 SCV001428434 uncertain significance Usher syndrome 2020-07-28 reviewed by expert panel curation The c.9433C>T (p.Leu3145Phe) variant in USH2A is present in 0.0033% (1/30612) of South Asian allele in gnomAd v2.1.1 and in 0.0074% (1/13568) of Latino alleles in gnomAD v3 (PM2). This variant has been detected in 1 proband with bilateral sensorineural hearing loss in a homozygous state (PM3_Supporting, PMID: 26806561). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein (PP3 not met). In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: PM2, PM3_Supporting.
Invitae RCV001036584 SCV001199957 uncertain significance not provided 2019-12-31 criteria provided, single submitter clinical testing This sequence change replaces leucine with phenylalanine at codon 3145 of the USH2A protein (p.Leu3145Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in individual(s) with retinitis pigmentosa (PMID: 26806561, 26927203, 26667666). 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: "Tolerated"; PolyPhen-2: "Possibly 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.
Blueprint Genetics RCV001073325 SCV001238864 pathogenic Retinal dystrophy 2018-11-20 criteria provided, single submitter clinical testing

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