Submissions for variant NM_006005.3(WFS1):c.1525_1539del (p.Val509_Tyr513del)

dbSNP: rs781262017

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001941578	SCV002233027	pathogenic	not provided	2024-03-07	criteria provided, single submitter	clinical testing	This variant, c.1525_1539del, results in the deletion of 5 amino acid(s) of the WFS1 protein (p.Val509_Tyr513del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs781262017, gnomAD 0.01%). This variant has been observed in individual(s) with autosomal recessive Wolfram syndrome (PMID: 9771706, 25895475, 28432734). It has also been observed to segregate with disease in related individuals. This variant is also known as 1685del(CCTGCTCTATGTCTA) and del508YVYLL. ClinVar contains an entry for this variant (Variation ID: 1453842). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV001941578	SCV002559613	likely pathogenic	not provided	2024-09-11	criteria provided, single submitter	clinical testing	In-frame deletion of 5 amino acids in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23373429, 36098976, 9771706, 30352948, 33980734, 35452662, 35602877, 25895475, GosaliaH2023[Article], 28432734)
Fulgent Genetics, Fulgent Genetics	RCV002507696	SCV002816225	pathogenic	Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome	2022-04-26	criteria provided, single submitter	clinical testing
Department Of Endocrinology, Sanjay Gandhi Postgraduate Institute Of Medical Sciences	RCV002274237	SCV004025923	pathogenic	Wolfram syndrome 1	2023-08-15	criteria provided, single submitter	clinical testing	Homozygous 15 base pair deletion in exon 8 of the WFS1 gene (chr4:g.6301320_6301334del) that results in the in-frame deletion of 5 amino acids. The observed variation has previously been reported in patients affected with Wolfram syndrome. This variant has not been reported in the 1000 genomes and gnomAD databases. The reference region is conserved across species. PS1, PM1, PM2, PM4, PP3.
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	RCV003336476	SCV004046024	likely pathogenic	Autosomal dominant nonsyndromic hearing loss 6		criteria provided, single submitter	clinical testing	This variant is also referred to as 1685del(CCTGCTCTATGTCTA) or 1683-1697del15 in the literature. This 15 base pair in-frame deletion is found in exon 8 of 8, and it leads to the loss of five amino acid residues. This variant has been previously reported as a homozygous (PMID: 23373429, 9771706, Gupta et al. 2018) and heterozygous change (PMID: 25895475) in individuals with WFS1-related disorders. The c.1525_1539del (p.Val509_Tyr513del) variant is present in the heterozygous state in the gnomAD population database at a frequency of 0.004% (10/249648) and thus is presumed to be rare. Based on the available evidence, the c.1525_1539del (p.Val509_Tyr513del) variant is classified as Likely Pathogenic.
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV002274237	SCV005374459	pathogenic	Wolfram syndrome 1	2024-09-22	criteria provided, single submitter	clinical testing
OMIM	RCV002274237	SCV000024942	pathogenic	Wolfram syndrome 1	1998-10-01	no assertion criteria provided	literature only