Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Mayo Clinic Laboratories, |
RCV000660594 | SCV000782708 | uncertain significance | Seizures-scoliosis-macrocephaly syndrome | 2017-07-24 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000806392 | SCV000946387 | uncertain significance | Exostoses, multiple, type 2 | 2023-12-10 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 639 of the EXT2 protein (p.Thr639Met). This variant is present in population databases (rs138722406, gnomAD 0.01%). This missense change has been observed in individual(s) with EXT2-related conditions (PMID: 30997052). This variant is also known as c.2015C>T (p.Thr672Met). ClinVar contains an entry for this variant (Variation ID: 134205). 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 EXT2 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. |
Illumina Laboratory Services, |
RCV000806392 | SCV001259400 | likely benign | Exostoses, multiple, type 2 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. |
ITMI | RCV000120878 | SCV000085046 | not provided | not specified | 2013-09-19 | no assertion provided | reference population | |
OMIM | RCV000660594 | SCV000930614 | pathogenic | Seizures-scoliosis-macrocephaly syndrome | 2019-08-02 | no assertion criteria provided | literature only |