Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000466362 | SCV000541539 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2023-11-30 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 100 of the MAX protein (p.Arg100Cys). This variant is present in population databases (rs762084527, gnomAD 0.0009%). 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: 404108). 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. |
| Ambry Genetics | RCV002436378 | SCV002751457 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-09-29 | criteria provided, single submitter | clinical testing | The p.R100C variant (also known as c.298C>T), located in coding exon 5 of the MAX gene, results from a C to T substitution at nucleotide position 298. The arginine at codon 100 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration was detected in 1/102 Asian children diagnosed with a tumor under the age of 18 who underwent whole exome sequencing (Chan SH et al, NPJ Genom Med. 2018 Nov;3:30). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |