Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001774403 | SCV002002245 | uncertain significance | not provided | 2023-10-27 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation as the last 28 amino acids are lost, although loss-of-function variants have not been reported downstream of this position in the protein; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 20829227) |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003317525 | SCV004021040 | uncertain significance | not specified | 2023-06-23 | criteria provided, single submitter | clinical testing | Variant summary: TUBB3 c.1267C>T (p.Gln423X) results in a premature termination codon and is predicted to cause a truncation of the encoded protein, which is a commonly known mechanism for disease. Although the variant is not expected to cause absence of the protein through nonsense mediated decay, the variant is predicted to disrupt the last 27 amino acids in the protein sequence. To our knowledge, no pathogenic variants have been reported downstream of this truncation. The variant was absent in 251260 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1267C>T in individuals affected with Cortical Dysplasia, Complex, With Other Brain Malformations 1 and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter has assessed the variant since 2014, and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |