ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.2191A>G (p.Met731Val)

gnomAD frequency: 0.00001  dbSNP: rs144010362
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002521464 SCV003525508 uncertain significance not provided 2023-07-10 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 731 of the WFS1 protein (p.Met731Val). This variant is present in population databases (rs144010362, 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: 374399). 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 RCV000415192 SCV003802909 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 rs144010362 in Wolfram's syndrome yet.
Baylor Genetics RCV000415192 SCV000328753 uncertain significance Wolfram syndrome 1 2014-09-24 no assertion criteria provided clinical testing Our laboratory reported dual molecular diagnoses in ACTG1 (NM_001199954.1, c.118C>T) and WFS1 (NM_001145853.1, c.2191A>G and c.1079G>A in trans) in one individual with reported features of delayed motor milestones, delayed speech, mild intellectual disability, congenital bilateral sensorineural hearing loss, dysmorphic features and eye anomalies (strabismus, possible cortical visual impairment). Brain MRI showed dysplastic corpus callosum and possible intracranial lipoma.

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