Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001576124 | SCV001204102 | pathogenic | not provided | 2023-12-11 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 223 of the FGFR3 protein (p.Arg223Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of FGFR3-related conditions (PMID: 31976144; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 838879). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is expected to disrupt FGFR3 function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV001576124 | SCV001803248 | pathogenic | not provided | 2023-06-14 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 31976144) |
Blueprint Genetics | RCV001576124 | SCV001832473 | likely pathogenic | not provided | 2019-11-30 | criteria provided, single submitter | clinical testing | |
3billion | RCV002283520 | SCV002573207 | likely pathogenic | Muenke syndrome | 2022-09-01 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.64; 3Cnet: 0.94). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000838879). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. |