ClinVar Miner

Submissions for variant NM_017890.4(VPS13B):c.11314C>T (p.Gln3772Ter) (rs386834061)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000415410 SCV000492975 pathogenic Short stature; Retinal dystrophy; Microcephaly; Progressive visual loss; Intellectual disability; Short foot; Neutropenia; Recurrent aphthous stomatitis; Small hand 2014-11-07 criteria provided, single submitter clinical testing
GeneDx RCV000599109 SCV000709905 pathogenic not provided 2018-12-04 criteria provided, single submitter clinical testing The Q3772X variant in the VPS13B gene has been reported previously in association with Cohen syndrome, in an affected individual who was heterozygous for the Q3772X variant and another variant (Hennies et al., 2004). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Q3772X variant is not observed in large population cohorts (Lek et al., 2016). We interpret Q3772X as a pathogenic variant.
Integrated Genetics/Laboratory Corporation of America RCV000050048 SCV000918353 likely pathogenic Cohen syndrome 2018-11-05 criteria provided, single submitter clinical testing Variant summary: VPS13B c.11314C>T (p.Gln3772X) 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. The variant was absent in 277252 control chromosomes. c.11314C>T has been reported in the literature in individuals affected with Cohen Syndrome (Hennies_2004, Katzaki_2007) . These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000050048 SCV000082457 probable-pathogenic Cohen syndrome no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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