Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001561278 | SCV001783842 | likely pathogenic | not provided | 2023-06-22 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); Canonical splice site variant predicted to result in an in-frame loss of the adjacent exon in a gene for which loss of function is a known mechanism of disease |
Invitae | RCV001882653 | SCV002300715 | likely pathogenic | Hypogonadotropic hypogonadism 2 with or without anosmia; Pfeiffer syndrome | 2024-01-04 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 4 of the FGFR1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in FGFR1 are known to be pathogenic (PMID: 12627230). This variant is present in population databases (rs376416531, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with FGFR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1197448). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
Fulgent Genetics, |
RCV002476862 | SCV002792828 | likely pathogenic | Hypogonadotropic hypogonadism 2 with or without anosmia; Jackson-Weiss syndrome; Pfeiffer syndrome; Hartsfield-Bixler-Demyer syndrome; Osteoglophonic dysplasia; Trigonocephaly 1; Encephalocraniocutaneous lipomatosis | 2021-12-21 | criteria provided, single submitter | clinical testing | |
Ce |
RCV001561278 | SCV004164642 | uncertain significance | not provided | 2023-09-01 | criteria provided, single submitter | clinical testing | FGFR1: PM2, PVS1:Supporting |