Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV001002536 | SCV001160499 | uncertain significance | not specified | 2019-05-03 | criteria provided, single submitter | clinical testing | The FGFR1 c.1694C>T; p.Ser565Phe variant (rs768223019), to our knowledge, is not described in the medical literature or in gene-specific databases, and is observed on only 1 allele in the Genome Aggregation Database. The serine at codon 565 is moderately conserved, and computational algorithms (PolyPhen-2, SIFT) predict that this variant is deleterious. However, due to the lack of clinical and functional data regarding this variant, its clinical significance cannot be determined with certainty. |
Baylor Genetics | RCV001332494 | SCV001524835 | uncertain significance | Encephalocraniocutaneous lipomatosis | 2019-10-25 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
Labcorp Genetics |
RCV001860516 | SCV002286567 | uncertain significance | Hypogonadotropic hypogonadism 2 with or without anosmia; Pfeiffer syndrome | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 565 of the FGFR1 protein (p.Ser565Phe). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 811993). 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 FGFR1 protein function with a positive predictive value of 80%. 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. |