Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mayo Clinic Laboratories, |
RCV000660595 | SCV000782709 | uncertain significance | Seizures-scoliosis-macrocephaly syndrome | 2017-07-24 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV001104529 | SCV001261402 | uncertain significance | 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Labcorp Genetics |
RCV001104529 | SCV004300863 | uncertain significance | Exostoses, multiple, type 2 | 2023-01-13 | criteria provided, single submitter | clinical testing | This variant is also known as c.1118T>A (p.Val373Asp). 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. 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. ClinVar contains an entry for this variant (Variation ID: 547989). This missense change has been observed in individual(s) with clinical features of autosomal recessive EXT2-related conditions (PMID: 30997052). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs371996957, gnomAD 0.003%). This sequence change replaces valine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 340 of the EXT2 protein (p.Val340Asp). |
| OMIM | RCV000660595 | SCV000930613 | pathogenic | Seizures-scoliosis-macrocephaly syndrome | 2019-08-02 | no assertion criteria provided | literature only |