Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001379449 | SCV001577252 | likely pathogenic | not provided | 2023-11-21 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 417 of the SLC4A11 protein (p.Gly417Arg). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individuals with congenital hereditary endothelial dystrophy (PMID: 23922488, 31714402). ClinVar contains an entry for this variant (Variation ID: 1068021). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SLC4A11 protein function. Experimental studies have shown that this missense change affects SLC4A11 function (PMID: 29327391). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001779160 | SCV002015156 | likely pathogenic | Corneal dystrophy-perceptive deafness syndrome | 2021-10-31 | criteria provided, single submitter | clinical testing | Variant summary: SLC4A11 c.1249G>A (p.Gly417Arg) results in a non-conservative amino acid change located in the Bicarbonate transporter, C-terminal domain (IPR011531) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.1e-06 in 247632 control chromosomes. c.1249G>A has been reported in the literature in multiple individuals affected with Congenital hereditary endothelial dystrophy 2 (CHED2) (example, Kodaganur_2013, Chaurasia_2020). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function as an ER-retained mutant with reduced cell surface abundance (Alka_2018). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Fulgent Genetics, |
RCV002488196 | SCV002783492 | likely pathogenic | Corneal dystrophy-perceptive deafness syndrome; Congenital hereditary endothelial dystrophy of cornea; Corneal dystrophy, Fuchs endothelial, 4 | 2021-11-02 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV001779160 | SCV002090946 | likely pathogenic | Corneal dystrophy-perceptive deafness syndrome | 2020-10-29 | no assertion criteria provided | clinical testing |