Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000220328 | SCV000273342 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-09-14 | criteria provided, single submitter | clinical testing | The p.A105V variant (also known as c.314C>T), located in coding exon 5 of the MAX gene, results from a C to T substitution at nucleotide position 314. The alanine at codon 105 is replaced by valine, an amino acid with similar properties. This amino acid position is highly conserved through mammals, but valine is the refence amino acid in several lower vertebrates. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV000792113 | SCV000931391 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2024-01-14 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 105 of the MAX protein (p.Ala105Val). This variant is present in population databases (rs769051095, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MAX-related conditions. ClinVar contains an entry for this variant (Variation ID: 229959). 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 tolerated. 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. |