Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002030008 | SCV002112580 | uncertain significance | Multiple congenital exostosis | 2023-12-10 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 469 of the EXT1 protein (p.Tyr469Cys). This variant is present in population databases (rs750748090, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with EXT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1346427). 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 EXT1 protein function. 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. |
| Ambry Genetics | RCV002543475 | SCV003538256 | uncertain significance | Inborn genetic diseases | 2022-05-27 | criteria provided, single submitter | clinical testing | The c.1406A>G (p.Y469C) alteration is located in exon 5 (coding exon 5) of the EXT1 gene. This alteration results from a A to G substitution at nucleotide position 1406, causing the tyrosine (Y) at amino acid position 469 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |