ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.2347T>C (p.Phe783Leu) (rs71526461)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000198824 SCV000252501 likely benign not specified 2014-11-19 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000198824 SCV000966803 uncertain significance not specified 2018-08-02 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Phe783Leu var iant in WFS1 has not been previously reported in individuals with hearing loss, but has been identified in 0.11% (12/10056) of Ashkenazi Jewish chromosomes and 11/18810 East Asian chromosomes by the Genome Aggregation Database (gnomAD, http ://gnomad.broadinstitute.org/). This variant has been reported in ClinVar (Varia tion ID: 211079). Phenylalanine (Phe) at position 783 is not conserved in mammal s or evolutionarily distant species and 16 species, including 2 mammals, carry a Leucine (Leu) at this position, raising the possibility that this change may be tolerated. Additional computational prediction tools suggest that the p.Phe783L eu variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, while the clinical significance o f the p.Phe783Leu variant is uncertain, these data suggest that it is more likel y to be benign. ACMG/AMP Criteria applied: BP4.
Illumina Clinical Services Laboratory,Illumina RCV001152301 SCV001313513 uncertain significance Autosomal dominant nonsyndromic deafness 6 2018-01-15 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 RCV001152302 SCV001313514 uncertain significance WFS1-Related Spectrum Disorders 2018-01-15 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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