Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000165082 | SCV000215785 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2014-08-01 | criteria provided, single submitter | clinical testing | The c.245_247delCTA variant (also known as p.T82del) located in coding exon 3 of the MLH1 gene. This variant results from an in-frame deletion of 3 nucleotides at positions 245 to 247 and the removal of a highly-conserved threonine residue at codon 82. T82 is an essential residue for establishing the nucleotide binding pocket and stabilization through hydrogen bonds to both the adenine base and the second phosphate of the bound nucleotide (Borrs E, Hum. Mutat. 2012 Nov; 33(11):1576-88). 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 0.004% (greater than 25,000 alleles tested) in our clinical cohort (includes this individual). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |