Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003112199 | SCV003786497 | pathogenic | Multiple congenital exostosis | 2024-01-19 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp364*) in the EXT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EXT1 are known to be pathogenic (PMID: 10679937, 11391482, 19810120). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with hereditary multiple osteochondromas (PMID: 30806661). ClinVar contains an entry for this variant (Variation ID: 2418955). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Lifecell International Pvt. |
RCV003157981 | SCV003845986 | likely pathogenic | Exostoses, multiple, type 1 | criteria provided, single submitter | clinical testing | A Heterozygous Nonsense variant c.1091G>A in Exon 3 of the EXT1 gene that results in the amino acid substitution p.Trp364* was identified. The observed variant is novel in gnomAD exomes and genomes, respectively. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score . Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. Based on the above evidence this variant has been classified as Likely Pathogenic according to the ACMG guidelines. |