ClinVar Miner

Submissions for variant NM_015404.4(WHRN):c.958C>T (p.Leu320Phe) (rs780855079)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001000529 SCV001157442 uncertain significance not specified 2018-10-09 criteria provided, single submitter clinical testing The WHRN c.958C>T; p.Leu320Phe variant (rs780855079), to our knowledge, has not been reported in the medical literature or gene specific databases. This variant is found in the general population with an allele frequency in non-Finnish Europeans of 0.0004% (8/111,704 alleles) in the Genome Aggregation Database. The leucine at codon 320 is highly conserved and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, based on the available information, the clinical significance of this variant is uncertain.
Invitae RCV001052821 SCV001217050 uncertain significance not provided 2020-01-08 criteria provided, single submitter clinical testing This sequence change replaces leucine with phenylalanine at codon 320 of the WHRN protein (p.Leu320Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is present in population databases (rs780855079, ExAC 0.009%). 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: "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.
Illumina Clinical Services Laboratory,Illumina RCV001168139 SCV001330710 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.
Illumina Clinical Services Laboratory,Illumina RCV001168140 SCV001330711 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.

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