Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002513104 | SCV003524025 | uncertain significance | not provided | 2022-10-17 | criteria provided, single submitter | clinical testing | 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 CD46 protein function. ClinVar contains an entry for this variant (Variation ID: 17049). This variant is also known as p.C1Y. This missense change has been observed in individual(s) with atypical hemolytic uremic syndrome (PMID: 2431077, 16621965, 24460647). This variant is present in population databases (rs121909591, gnomAD 0.007%). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 35 of the CD46 protein (p.Cys35Tyr). Studies have shown that this missense change alters CD46 gene expression (PMID: 16621965). 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. |
| 3billion | RCV000018577 | SCV003841781 | likely pathogenic | Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly | 2023-02-23 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.001%). Functional studies provide moderate evidence of the variant having a damaging effect on the gene or gene product (PMID: 16621965). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.88; 3Cnet: 0.81). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with CD46 related disorder (PMID: 16621965). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. |
| OMIM | RCV000018577 | SCV000038860 | risk factor | Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly | 2006-08-15 | no assertion criteria provided | literature only |