Submissions for variant NM_152564.5(VPS13B):c.5197dup (p.Glu1733fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002625685	SCV002951241	pathogenic	Cohen syndrome	2023-09-29	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu1758Glyfs*11) in the VPS13B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in VPS13B are known to be pathogenic (PMID: 15141358, 16648375, 20461111). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Cohen syndrome (PMID: 32170714). ClinVar contains an entry for this variant (Variation ID: 1917851). For these reasons, this variant has been classified as Pathogenic.
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV002625685	SCV005093875	pathogenic	Cohen syndrome		criteria provided, single submitter	clinical testing	This variant is likely to cause shift in the reading frame of the transcript which will either cause the transcript to undergo nonsense-mediated mRNA decay or formation of a truncated protein product. This variant has been reported in ClinVar (Accession ID: VCV001917851.3) as pathogenic. Biallelic disease-causing variants in VPS13B are known to cause Cohen syndrome. The clinical features seen in the first child of the couple overlaps with Cohen syndrome and this variant in homozygous state is interpreted to be the likely cause of clinical features seen in their child.