Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002408590 | SCV002676854 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-03 | criteria provided, single submitter | clinical testing | The p.N263T variant (also known as c.788A>C), located in coding exon 9 of the MLH1 gene, results from an A to C substitution at nucleotide position 788. The asparagine at codon 263 is replaced by threonine, an amino acid with similar properties. This variant has been detected in conjunction with two different synonymous MLH1 variants in a female diagnosed with MSI-H endometrial cancer exhibiting loss of MLH1 protein expression by immunohistochemistry who had a family history that fulfilled Amsterdam II criteria (Borràs E et al. Hum. Mutat., 2012 Nov;33:1576-88). Additionally, RNA studies suggested this variant may lead to coding exon 9 skipping; however, due to the two additional variants identified, the reported splicing defect could not be confirmed to be the result of this variant, the synonymous variants, or a combination of the variants (Borràs E et al. Hum. Mutat., 2012 Nov;33:1576-88). RNA studies have demonstrated that this alteration results in an incomplete splice defect; the clinical impact of this abnormal splicing is unknown at this time (Ambry internal data). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Harris Lab, |
RCV000114848 | SCV000148743 | not provided | not provided | no assertion provided | not provided |