Submissions for variant NM_152564.5(VPS13B):c.11338dup (p.Val3780fs)

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Total submissions: 3

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000674026	SCV000799296	likely pathogenic	Cohen syndrome	2018-04-09	criteria provided, single submitter	clinical testing
Invitae	RCV000674026	SCV001391858	pathogenic	Cohen syndrome	2022-07-05	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 557835). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with VPS13B-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val3805Glyfs*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).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000674026	SCV002500433	likely pathogenic	Cohen syndrome	2022-03-16	criteria provided, single submitter	clinical testing	Variant summary: VPS13B c.11413dupG (p.Val3805GlyfsX11) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory and have been reported in association with a phenotype of Cohen syndrome in the HGMD database. The variant was absent in 251374 control chromosomes. To our knowledge, no occurrence of c.11413dupG in individuals affected with Cohen Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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