Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003062274 | SCV003441442 | likely pathogenic | not provided | 2024-01-14 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1701 of the CDH23 protein (p.Glu1701Lys). This variant is present in population databases (rs764025875, gnomAD 0.01%). This missense change has been observed in individuals with deafness (PMID: 24416283, 29287849). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 2136884). 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) performed at Invitae indicates that this missense variant is expected to disrupt CDH23 protein function with a positive predictive value of 80%. 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. |
Baylor Genetics | RCV003475493 | SCV004210593 | likely pathogenic | Pituitary adenoma 5, multiple types | 2023-10-20 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV004526222 | SCV005040052 | likely pathogenic | Hereditary factor VIII deficiency disease | 2024-03-07 | criteria provided, single submitter | clinical testing | Variant summary: F8 c.5101G>A (p.Glu1701Lys) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 180470 control chromosomes. c.5101G>A has been reported in the literature in individuals affected with Factor VIII Deficiency (Hemophilia A). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. ClinVar contains an entry for this variant (Variation ID: 2683573). Based on the evidence outlined above, the variant was classified as likely pathogenic. |