Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001732716 | SCV001983258 | likely pathogenic | not provided | 2024-06-20 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23329143, 16757108, 20536592) |
| 3billion | RCV002051952 | SCV002318655 | likely pathogenic | Hartsfield-Bixler-Demyer syndrome | 2022-03-22 | criteria provided, single submitter | clinical testing | The variant has been observed in at least two similarly affected unrelated individuals (PMID: 16757108).A different missense change at the same codon has been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000265428, PMID:16757108). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.945>=0.6, 3CNET: 0.981>=0.75). A missense variant is a common mechanism. It is not observed in the gnomAD v2.1.1 dataset. Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. |
| Labcorp Genetics |
RCV003771891 | SCV004569698 | uncertain significance | Hypogonadotropic hypogonadism 2 with or without anosmia; Pfeiffer syndrome | 2022-11-22 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Arg622 amino acid residue in FGFR1. Other variant(s) that disrupt this residue have been observed in individuals with FGFR1-related conditions (PMID: 16757108), which suggests that this may be a clinically significant amino acid residue. 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. ClinVar contains an entry for this variant (Variation ID: 1300944). This missense change has been observed in individuals with clinical features of Kallmann syndrome (PMID: 20536592; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 622 of the FGFR1 protein (p.Arg622Gln). |