Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000222188 | SCV000276265 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2015-06-04 | criteria provided, single submitter | clinical testing | The p.I71N variant (also known as c.212T>A), located in coding exon 4 of the MAX gene, results from a T to A substitution at nucleotide position 212. The isoleucine at codon 71 is replaced by asparagine, an amino acid with dissimilar properties. This variant sits at the MAX-MYC dimerization interface and is anticipated to result in a significant decrease in structural stability (Ambry Internal Structural Analysis). Another alteration at this codon (p.I71S) has been reported in an individual with bilateral pheochromocytomas diagnosed at age 34y (Burnichon N, et al. Clin. Cancer Res. 2012 May; 18(10):2828-37). This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.02% (greater than 4500 alleles tested) in our clinical cohort. Based on protein sequence alignment, this amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |