ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.1467C>G (p.Ile489Met)

gnomAD frequency: 0.00003  dbSNP: rs768029820
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000520862 SCV000618490 uncertain significance not provided 2022-09-13 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV001198043 SCV001368828 uncertain significance Type 2 diabetes mellitus 2019-05-04 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The following ACMG criteria were applied in classifying this variant: PM2.
Labcorp Genetics (formerly Invitae), Labcorp RCV000520862 SCV002209269 uncertain significance not provided 2023-09-09 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 489 of the WFS1 protein (p.Ile489Met). This variant is present in population databases (rs768029820, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with WFS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 449979). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt WFS1 protein function. 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.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV003126789 SCV003801371 likely benign Wolfram syndrome 1 criteria provided, single submitter research Potent mutations in WFS1 gene are associated with Wolfram's syndrome, an autosomal recessive condition, which cause diabetes mellitus, diabetes insipidus, deafness and optic atrophy. However no sufficient evidence is found to ascertain the role of this particular variant rs768029820 in Wolfram's syndrome yet.

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