ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.1234G>C (p.Val412Leu)

gnomAD frequency: 0.00001  dbSNP: rs149865710
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001155662 SCV001317110 likely benign Autosomal dominant nonsyndromic hearing loss 6 2017-06-20 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. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina RCV001155663 SCV001317111 uncertain significance WFS1-Related Spectrum Disorders 2017-06-20 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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV001195409 SCV001365759 uncertain significance not specified 2019-08-12 criteria provided, single submitter clinical testing The p.Val412Leu variant in WFS1 has not been previously reported in individuals with hearing loss, Wolfram syndrome, or Wolfram-like syndrome. It has been identified in 0.097% (18/18392) of East Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant has also been reported in ClinVar (Variation ID 143131). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: BS1_Supporting.
GeneDx RCV000132655 SCV001770501 uncertain significance not provided 2020-10-01 criteria provided, single submitter clinical testing Observed in individuals with type 1 or type 2 diabetes and in individuals with hearing loss, but also observed in control groups (Kawamoto et al., 2004; Fukuoka et al., 2007; Awata et al., 2013); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 17492394, 23856252, 15234338)
Invitae RCV000132655 SCV002491292 likely benign not provided 2024-01-04 criteria provided, single submitter clinical testing
Department of Ophthalmology and Visual Sciences Kyoto University RCV000132655 SCV000172606 probable-non-pathogenic not provided no assertion criteria provided not provided Converted during submission to Likely benign.

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