ClinVar Miner

Submissions for variant NM_015404.4(WHRN):c.191C>A (p.Ala64Asp) (rs146655362)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000038882 SCV000062560 likely benign not specified 2012-12-28 criteria provided, single submitter clinical testing Ala64Asp in exon 1 of DFNB31: This variant is not expected to have clinical sign ificance because it has been identified in 0.2% (15/8598) of European American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS/; dbSNP rs146655362).
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000723700 SCV000113670 uncertain significance not provided 2013-08-16 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000291435 SCV000476806 uncertain significance Usher syndrome, type 2D 2018-01-12 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 RCV000346369 SCV000476807 uncertain significance Deafness, autosomal recessive 31 2018-01-12 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 RCV000723700 SCV001208506 uncertain significance not provided 2019-12-11 criteria provided, single submitter clinical testing This sequence change replaces alanine with aspartic acid at codon 64 of the WHRN protein (p.Ala64Asp). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and aspartic acid. This variant is present in population databases (rs146655362, ExAC 0.1%). This variant has not been reported in the literature in individuals with WHRN-related conditions. 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.
Division of Human Genetics,Children's Hospital of Philadelphia RCV000477861 SCV000536781 uncertain significance Deafness, autosomal recessive 31; Usher syndrome, type 2D 2015-10-13 no assertion criteria provided research

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