ClinVar Miner

Submissions for variant NM_000100.3(CSTB):c.136C>T (p.Gln46Ter) (rs545986367)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187279 SCV000240861 pathogenic not provided 2016-04-13 criteria provided, single submitter clinical testing The Q46X nonsense variant in the CSTB gene has been reported previously in an individual with Unverricht-Lundborg disease who was compound heterozygous for Q46X and the common dodecamer repeat expansion (Canafoglia et al., 2012). This pathogenic variant is predicted to cause loss of normal protein function through protein truncation as the last 53 amino acids of the CSTB protein are lost. Furthermore, the Q46X variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, and it was not observed with any significant frequency in the 1000 Genomes Project. Therefore, Q46X is considered a pathogenic variant.
Ambry Genetics RCV000622652 SCV000741948 pathogenic Inborn genetic diseases 2017-06-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: LIKELY POSITIVE: Relevant Alteration(s) Detected
Invitae RCV000811370 SCV000951632 pathogenic Progressive myoclonic epilepsy 2018-12-13 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the CSTB gene (p.Gln46*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 53 amino acids of the CSTB protein. This variant is present in population databases (rs545986367, ExAC 0.03%). This variant has been observed in an individual with CTSB-related progressive myoclonic epilepsy (PMID: 23205931). This variant is also known as c.133C>T in the literature. ClinVar contains an entry for this variant (Variation ID: 161418). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. This variant disrupts the C-terminus of the CSTB protein. Other variant(s) that disrupt this region (p.Arg68*) have been determined to be pathogenic (PMID:26843564, 8596935, 15483648). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
GeneReviews RCV000202565 SCV000195826 pathogenic Unverricht-Lundborg syndrome 2014-11-25 no assertion criteria provided literature only

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