Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000215214 | SCV000274165 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-12-22 | criteria provided, single submitter | clinical testing | The c.677+3A>T intronic pathogenic mutation results from an A to T substitution 3 nucleotides after coding exon 8 in the MLH1 gene. This variant has been reported in the literature in a Danish HNPCC registry cohort and was demonstrated to result in coding exon 8 skipping (Petersen S et al. BMC Med. Genet. 2013 Oct;14:103; Ambry internal data). Another alteration impacting the same donor site (c.677+3A>G) has been identified in multiple individuals with personal and/or family history consistent with Lynch syndrome (Casey G et al JAMA. 2005 Feb 16;293(7):799-809; Kruger S et al Hum Mutat. 2003 Apr;21(4):445-6), and has also been shown to result in exon skipping, and premature protein truncation in functional analyses (Betz B et al J Cancer Res Clin Oncol. 2010 Jan;136(1):123-34; Naruse H et al Fam Cancer. 2009;8(4):509-17). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may weaken the native splice donor site and may result in the creation or strengthening of a novel splice donor site. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
| Myriad Genetics, |
RCV003454619 | SCV004186526 | pathogenic | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-07-17 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. Functional studies indicate this variant impacts protein function [PMID: 12655562]. |
| Baylor Genetics | RCV003454619 | SCV004193047 | uncertain significance | Colorectal cancer, hereditary nonpolyposis, type 2 | 2022-06-18 | criteria provided, single submitter | clinical testing |