ClinVar Miner

Submissions for variant NM_152564.5(VPS13B):c.5923_5924del (p.Leu1975fs)

dbSNP: rs886041323
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000324904 SCV000329733 pathogenic not provided 2016-08-23 criteria provided, single submitter clinical testing The c.5998_5999delCT pathogenic variant in the VPS13B gene has been reported previously in association with Cohen syndrome (Madrigal et al., 2014). This variant causes a frameshift starting with codon Leucine 2000, changes this amino acid to an Alanine residue, and creates a premature Stop codon at position 2 of the new reading frame, denoted p.Leu2000AlafsX2. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.5998_5999delCT variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.5998_5999delCT as a pathogenic variant.
Invitae RCV000411379 SCV000932734 pathogenic Cohen syndrome 2023-12-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu2000Alafs*2) 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 present in population databases (no rsID available, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with Cohen syndrome (PMID: 25271213). ClinVar contains an entry for this variant (Variation ID: 280018). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000411379 SCV000486592 likely pathogenic Cohen syndrome 2016-06-28 no assertion criteria provided clinical testing
Natera, Inc. RCV000411379 SCV002082595 pathogenic Cohen syndrome 2021-04-12 no assertion criteria provided clinical testing

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