ClinVar Miner

Submissions for variant NM_003165.4(STXBP1):c.1162C>T (p.Arg388Ter) (rs121918321)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189612 SCV000243257 pathogenic not provided 2018-05-29 criteria provided, single submitter clinical testing The R388X pathogenic nonsense variant in the STXBP1 gene has been reported previously occurring de novo with confirmed parentage in a patient with intellectual disability with nonsyndromic epilepsy (Hamdan et al., 2009). It was subsequently reported as a de novo pathogenic variant in a patient with ataxia-tremor-retardation syndrome who did not have a history of seizures (Gburek-Augustat et al., 2016). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R388X variant is not observed in large population cohorts (Lek et al., 2016). Therefore, R388X is interpreted to be a pathogenic variant and its presence is consistent with the diagnosis of a STXBP1-related disorder in this individual.
Invitae RCV000539734 SCV000633886 pathogenic Early infantile epileptic encephalopathy 2019-05-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg388*) in the STXBP1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in individuals affected with Ohtahara syndrome (PMID: 26514728), intellectual disability with epilepsy (PMID: 19557857), and intellectual disability without epilepsy (PMID: 27184330). ClinVar contains an entry for this variant (Variation ID: 6730). Loss-of-function variants in STXBP1 are known to be pathogenic (PMID: 20887364, 26384463). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000007122 SCV000027318 pathogenic Early infantile epileptic encephalopathy 4 2009-06-01 no assertion criteria provided literature only
GeneReviews RCV000007122 SCV000494040 pathogenic Early infantile epileptic encephalopathy 4 2016-09-09 no assertion criteria provided literature only

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