Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000413114 | SCV000490477 | likely pathogenic | not provided | 2016-09-29 | criteria provided, single submitter | clinical testing | The E330K variant in the CLTCL1 gene has been reported previously, in the homozygous state, in three siblingswith significant intellectual disability, global developmental delay, absent pain sensation, self mutilating behavior,ophthalmological abnormalities, hypotonia, bone abnormalities, dysmorphic features, and brain abnormalities onMRI, with childhood death in two of the three siblings (Nahorski et al., 2015). The variant has also been reported inthe presence of another CLTCL1 variant in one individual with autism (Chahrour et al., 2012). The E330K variantwas not observed with any significant frequency in approximately 6200 individuals of European and African Americanancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in thesepopulations. The E330K variant is a non-conservative amino acid substitution, which is likely to impact secondaryprotein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at aposition that is conserved across species and in silico analysis predicts this variant is probably damaging to theprotein structure/function. Therefore, we interpret E330K as a likely pathogenic variant, however, the possibility itmay be a rare benign variant cannot be excluded. |
| OMIM | RCV000413114 | SCV000490245 | uncertain significance | not provided | 2015-10-29 | no assertion criteria provided | literature only |