Submissions for variant NM_152564.5(VPS13B):c.3866C>G (p.Thr1289Ser)

gnomAD frequency: 0.00178  dbSNP: rs145569846

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000081898	SCV000113833	uncertain significance	not provided	2013-10-04	criteria provided, single submitter	clinical testing
Invitae	RCV000530711	SCV000630874	likely benign	Cohen syndrome	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002311681	SCV000847118	likely benign	Inborn genetic diseases	2018-09-26	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000530711	SCV000899082	uncertain significance	Cohen syndrome	2021-09-17	criteria provided, single submitter	clinical testing	VPS13B NM_017890.4 exon 25 p.Thr1289Ser (c.3866C>G): This variant has been reported in the literature as a compound heterozygote (in trans with a multi-exon deletion of this gene) in 1 individual with a diagnosis of Cohen syndrome (Rivera-Brugues 2011 PMID:20921020, gene identified as alternate name COH1). However, this variant is present in 0.5% (125/24018) of African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs145569846). This variant is present in ClinVar (Variation ID:95851). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Mendelics	RCV000530711	SCV001137683	benign	Cohen syndrome	2023-08-22	criteria provided, single submitter	clinical testing
GeneDx	RCV000081898	SCV001779477	likely benign	not provided	2020-10-14	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 20921020)
Revvity Omics, Revvity	RCV000530711	SCV003820434	uncertain significance	Cohen syndrome	2019-08-06	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000530711	SCV001456848	likely benign	Cohen syndrome	2020-09-16	no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000081898	SCV001958134	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000081898	SCV001975329	uncertain significance	not provided		no assertion criteria provided	clinical testing