ClinVar Miner

Submissions for variant NM_015404.4(WHRN):c.2056C>A (p.Pro686Thr) (rs201690920)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000038884 SCV000062562 uncertain significance not specified 2016-01-19 criteria provided, single submitter clinical testing The p.Pro686Thr variant in DFNB31 has been previously identified by our laborato ry in 1 Hispanic individual with hearing loss; however, a variant on the remaini ng copy of DFNB31 has not been identified. It has been identified in 10/11564 La tino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadins titute.org; dbSNP rs201690920). Although this variant has been seen in the gene ral population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical signif icance of the p.Pro686Thr variant is uncertain.
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000038884 SCV000258086 uncertain significance not specified 2015-05-05 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001169778 SCV001332551 uncertain significance Usher syndrome, type 2D 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Clinical Services Laboratory,Illumina RCV001169779 SCV001332552 uncertain significance Deafness, autosomal recessive 31 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae RCV001233944 SCV001406564 uncertain significance not provided 2019-08-05 criteria provided, single submitter clinical testing This sequence change replaces proline with threonine at codon 686 of the WHRN protein (p.Pro686Thr). The proline residue is highly conserved and there is a small physicochemical difference between proline and threonine. This variant is present in population databases (rs201690920, ExAC 0.09%). This variant has not been reported in the literature in individuals with WHRN-related disease. ClinVar contains an entry for this variant (Variation ID: 45666). Algorithms developed to predict the effect of missense changes on protein structure and function 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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