Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000491989 | SCV000580095 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-04-22 | criteria provided, single submitter | clinical testing | The c.3999dupT pathogenic mutation, located in coding exon 9 of the MSH6 gene, results from a duplication of T at nucleotide position 3999, causing a translational frameshift with a predicted alternate stop codon (p.R1334Sfs*7). This alteration had been identified in individuals with MSH6-deficient colon and/or endometrial cancers (Ambry internal data). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation. |
Color Diagnostics, |
RCV000491989 | SCV000904029 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2019-04-05 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001853255 | SCV002231784 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-10-27 | criteria provided, single submitter | clinical testing | This premature translational stop signal has been observed in individuals with personal and family history of Lynch syndrome-associated tumors (external communication). For these reasons, this variant has been classified as Pathogenic. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 218076). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg1334Serfs*7) in the MSH6 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 27 amino acid(s) of the MSH6 protein. |
Mayo Clinic Laboratories, |
RCV000202009 | SCV000257293 | likely pathogenic | not provided | no assertion criteria provided | clinical testing |