Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000199533 | SCV000251014 | likely pathogenic | not provided | 2014-12-16 | criteria provided, single submitter | clinical testing | p.Gly291Ser (GGT>AGT): c.871 G>A in exon 7 of the ABCB7 gene (NM_004299.3). The G291S variant that is likely pathogenic was identified in the ABCB7 gene. It has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The G291S variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G291S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is highly conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, this variant is a strong candidate for a pathogenic mutation, however the possibility that it is a benign variant cannot be excluded. The variant is found in MITONUC-MITOP panel(s). |
| Labcorp Genetics |
RCV000199533 | SCV004620949 | uncertain significance | not provided | 2023-12-11 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 291 of the ABCB7 protein (p.Gly291Ser). This variant is present in population databases (no rsID available, gnomAD 0.003%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with ABCB7-related conditions. ClinVar contains an entry for this variant (Variation ID: 213988). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |