ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.1943G>T (p.Trp648Leu)

dbSNP: rs150465110
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000038648 SCV000062326 uncertain significance not specified 2013-01-17 criteria provided, single submitter clinical testing The Trp648Leu variant in WFS1 has not been reported in the literature nor previo usly identified by our laboratory. Computational analyses (biochemical amino aci d properties, conservation, AlignGVGD, PolyPhen2, and SIFT) provide inconsistent predictions on the impact of the variant on the protein. Therefore, additional data is needed to determine the clinical significance of this variant.
Fulgent Genetics, Fulgent Genetics RCV002490526 SCV002781755 uncertain significance Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2021-07-27 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003546463 SCV004250949 uncertain significance not provided 2023-05-18 criteria provided, single submitter clinical testing 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on WFS1 protein function. ClinVar contains an entry for this variant (Variation ID: 45444). This variant has not been reported in the literature in individuals affected with WFS1-related conditions. This variant is present in population databases (rs150465110, gnomAD 0.002%). This sequence change replaces tryptophan, which is neutral and slightly polar, with leucine, which is neutral and non-polar, at codon 648 of the WFS1 protein (p.Trp648Leu).
Ambry Genetics RCV004018878 SCV004979916 uncertain significance Inborn genetic diseases 2023-11-14 criteria provided, single submitter clinical testing The c.1943G>T (p.W648L) alteration is located in exon 8 (coding exon 7) of the WFS1 gene. This alteration results from a G to T substitution at nucleotide position 1943, causing the tryptophan (W) at amino acid position 648 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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