Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000074799 | SCV000108010 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000074799 | SCV000052933 | pathogenic | Lynch syndrome | 2011-08-18 | criteria provided, single submitter | curation | Converted during submission to Pathogenic. |
| Ambry Genetics | RCV001018330 | SCV001179554 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-02-10 | criteria provided, single submitter | clinical testing | The c.3053_3054delTC pathogenic mutation, located in coding exon 4 of the MSH6 gene, results from a deletion of two nucleotides at nucleotide positions 3053 to 3054, causing a translational frameshift with a predicted alternate stop codon (p.L1018Hfs*4). This alteration has been seen in families meeting Amsterdam criteria (Huang J et al. Cancer Res., 2001 Feb;61:1619-23; Lagerstedt Robinson K et al. J. Natl. Cancer Inst., 2007 Feb;99:291-9; Ambry internal data). Of note, this alteration is also designated as 3052delCT and c.3052_3053delCT in published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Invitae | RCV002514331 | SCV003524586 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-06-08 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu1018Hisfs*4) in the MSH6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). This premature translational stop signal has been observed in individual(s) with clinical features of MSH6-related conditions (PMID: 11245474). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 89334). This variant is not present in population databases (gnomAD no frequency). |
| Myriad Genetics, |
RCV000009489 | SCV004185911 | pathogenic | Lynch syndrome 5 | 2023-08-22 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
| Baylor Genetics | RCV003460675 | SCV004197730 | pathogenic | Endometrial carcinoma | 2023-09-13 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000009489 | SCV000029707 | pathogenic | Lynch syndrome 5 | 2001-02-15 | no assertion criteria provided | literature only |