Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002236439 | SCV002507620 | uncertain significance | not provided | 2023-08-23 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 423 of the FGFR3 protein (p.Val423Leu). This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with FGFR3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1680065). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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 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, |
RCV002481042 | SCV002784096 | uncertain significance | Achondroplasia; Camptodactyly-tall stature-scoliosis-hearing loss syndrome; Cervical cancer; Crouzon syndrome-acanthosis nigricans syndrome; Levy-Hollister syndrome; Muenke syndrome; Thanatophoric dysplasia type 1; Thanatophoric dysplasia, type 2; Malignant tumor of urinary bladder; Hypochondroplasia; Epidermal nevus; Severe achondroplasia-developmental delay-acanthosis nigricans syndrome; Colorectal cancer; Germ cell tumor of testis | 2021-08-31 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003101303 | SCV003716213 | uncertain significance | Inborn genetic diseases | 2021-04-09 | criteria provided, single submitter | clinical testing | The c.1267G>C (p.V423L) alteration is located in exon 10 (coding exon 9) of the FGFR3 gene. This alteration results from a G to C substitution at nucleotide position 1267, causing the valine (V) at amino acid position 423 to be replaced by a leucine (L). Based on data from the Genome Aggregation Database (gnomAD) database, the FGFR3 c.1267G>C alteration was observed in 0.0006% (1/156132) of total alleles studied. The p.V423 amino acid is conserved in available vertebrate species. The in silico prediction for the p.V423L alteration is inconclusive. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |