Submissions for variant NM_006005.3(WFS1):c.599T>C (p.Leu200Pro)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV002291963	SCV002584093	uncertain significance	not provided	2024-04-15	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23981289)
Labcorp Genetics (formerly Invitae), Labcorp	RCV002291963	SCV003525413	uncertain significance	not provided	2023-02-15	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). 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: 1710676). This missense change has been observed in individual(s) with Wolfram syndrome (PMID: 23981289). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 200 of the WFS1 protein (p.Leu200Pro).