Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003557758 | SCV004294246 | pathogenic | not provided | 2022-12-22 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with cornea plana (PMID: 28677912; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant is present in population databases (rs758552587, gnomAD 0.009%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 70 of the KERA protein (p.Pro70Leu). |
Prevention |
RCV004758942 | SCV005344782 | uncertain significance | KERA-related disorder | 2024-04-03 | no assertion criteria provided | clinical testing | The KERA c.209C>T variant is predicted to result in the amino acid substitution p.Pro70Leu. This variant was reported in a compound heterozygous state in an individual with Cornea plana (Dudakova et al 2018. PubMed ID: 28677912). This variant is reported in 0.0087% of alleles in individuals of Latino descent in gnomAD.. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |