Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001935567 | SCV002189349 | uncertain significance | Hypogonadotropic hypogonadism 2 with or without anosmia; Pfeiffer syndrome | 2024-01-14 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 756 of the FGFR1 protein (p.Arg756His). This variant is present in population databases (rs374473310, gnomAD 0.003%). This missense change has been observed in individual(s) with Chiari 1 malformation and/or hypothalamic amenorrhea (PMID: 21247312, 33337535). ClinVar contains an entry for this variant (Variation ID: 1416171). 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 FGFR1 protein function. Experimental studies have shown that this missense change affects FGFR1 function (PMID: 21247312). 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. |
| Fulgent Genetics, |
RCV002491888 | SCV002776725 | uncertain significance | Hypogonadotropic hypogonadism 2 with or without anosmia; Jackson-Weiss syndrome; Pfeiffer syndrome; Hartsfield-Bixler-Demyer syndrome; Osteoglophonic dysplasia; Trigonocephaly 1; Encephalocraniocutaneous lipomatosis | 2021-10-23 | criteria provided, single submitter | clinical testing |