ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.3584G>T (p.Cys1195Phe) (rs727504652)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000155915 SCV000205626 uncertain significance not specified 2013-09-27 criteria provided, single submitter clinical testing The Cys1195Phe variant in USH2A has not been previously reported in individuals with hearing loss or in large population studies. Computational analyses (bioch emical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do n ot provide strong support for or against an impact to the protein. In summary, a dditional data is needed to determine the clinical significance of this variant.
Counsyl RCV000668970 SCV000793656 uncertain significance Usher syndrome, type 2A; Retinitis pigmentosa 39 2017-08-22 criteria provided, single submitter clinical testing
Blueprint Genetics RCV000225490 SCV001240459 uncertain significance Retinal dystrophy 2019-07-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001098833 SCV001255224 uncertain significance Usher syndrome, type 2A 2018-01-18 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001098834 SCV001255225 uncertain significance Retinitis pigmentosa 2018-01-18 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Invitae RCV001227048 SCV001399384 uncertain significance not provided 2019-10-12 criteria provided, single submitter clinical testing This sequence change replaces cysteine with phenylalanine at codon 1195 of the USH2A protein (p.Cys1195Phe). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual with clinical features of Usher syndrome (PMID: 27208204). ClinVar contains an entry for this variant (Variation ID: 179130). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The phenylalanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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.
Centre for Genomic Medicine, Manchester,Central Manchester University Hospitals RCV000225490 SCV000282650 uncertain significance Retinal dystrophy no assertion criteria provided clinical testing

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