Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000293652 | SCV000382630 | likely benign | Porencephaly 2 | 2018-01-12 | 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. |
| Invitae | RCV001859864 | SCV002193588 | uncertain significance | not provided | 2023-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 403 of the COL4A2 protein (p.Pro403Leu). This variant is present in population databases (rs772448912, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with COL4A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 311121). 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 not expected to disrupt COL4A2 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 | RCV002522267 | SCV003638730 | uncertain significance | Inborn genetic diseases | 2022-08-02 | criteria provided, single submitter | clinical testing | The c.1208C>T (p.P403L) alteration is located in exon 20 (coding exon 19) of the COL4A2 gene. This alteration results from a C to T substitution at nucleotide position 1208, causing the proline (P) at amino acid position 403 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |