Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000187897 | SCV000241499 | uncertain significance | not provided | 2012-03-08 | criteria provided, single submitter | clinical testing | p.Leu391Pro (CTG>CCG): c.1172 T>C in exon 10 of the KCNQ2 gene. The Leu391Pro missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI ESP Exome Variant Project has not identified Leu391Pro in approximately 5,000 individuals of European or African American ethnicity, indicating that it is not a common benign variant in these populations. Although both Leucine and Proline are non-polar amino acids, the gain of a bulky Proline residue may alter the secondary structure of the protein. The Leu391Pro substitution alters a highly conserved position in the C-terminal domain of the KCNQ2 protein, and multiple in silico algorithms predict that Leu391Pro is damaging to protein structure/function. However, the majority of pathogenic missense mutations in this region map to one of the calmodulin (CaM) binding domains, whereas the Leu391 residue is not located in a CaM domain. Therefore, based on the information currently available, it is unclear whether Leu391Pro is a disease-causing mutation or a rare benign variant. The variant is found in INFANT-EPI panel(s). |