Submissions for variant NM_006005.3(WFS1):c.325C>T (p.His109Tyr)

gnomAD frequency: 0.00029  dbSNP: rs112871383

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000152664	SCV000202020	uncertain significance	not specified	2013-10-17	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The His109Tyr varia nt in WFS1 has not been reported in individuals with hearing loss, but has been identified in 1.0% (2/192) Luhya West African chromosomes by the 1000 Genomes Pr oject and in 0.04% (2/4402) of African American chromosomes by the NHLBI Exome S equencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs112871383). Compu tational analyses (biochemical amino acid properties, conservation, AlignGVGD, P olyPhen2, and SIFT) suggest that the His109Tyr variant may not impact the protei n, though this information is not predictive enough to rule out pathogenicity. I n summary, the clinical significance of this variant cannot be determined with c ertainty; however based upon its presence in the general population and the comp utational data, we would lean towards a more likely benign role.
GeneDx	RCV000727284	SCV000521494	likely benign	not provided	2020-08-31	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 12955714)
Eurofins Ntd Llc (ga)	RCV000727284	SCV000707224	uncertain significance	not provided	2017-04-17	criteria provided, single submitter	clinical testing
Personalized Diabetes Medicine Program, University of Maryland School of Medicine	RCV000664085	SCV000787537	uncertain significance	Monogenic diabetes	2017-06-01	criteria provided, single submitter	research	ACMG Criteria:PP3 (6 predictors), BP4 (3 predictors)
CeGaT Center for Human Genetics Tuebingen	RCV000727284	SCV001154157	uncertain significance	not provided	2019-05-01	criteria provided, single submitter	clinical testing
Invitae	RCV000727284	SCV001706142	likely benign	not provided	2023-12-01	criteria provided, single submitter	clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002509041	SCV002769836	uncertain significance	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 rs112871383 in Wolfram's syndrome yet.
Ambry Genetics	RCV002516064	SCV003681021	uncertain significance	Inborn genetic diseases	2021-09-13	criteria provided, single submitter	clinical testing	Unlikely to be causative of autosomal dominant WFS1-related Wolfram syndrome (AD) Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.