Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000204888 | SCV000261212 | pathogenic | Lynch syndrome | 2015-10-14 | criteria provided, single submitter | clinical testing | This sequence change deletes 5 nucleotides and inserts 1 nucleotide in exon 4 of the MSH6 mRNA (c.2308_2312delGGTAAinsT), causing a frameshift at codon 770. This creates a premature translational stop signal (p.Gly770Cysfs*4) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, truncating variants in MSH6 are known to be pathogenic (PMID: 24362816, 18269114). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV000218163 | SCV000278176 | pathogenic | Hereditary cancer-predisposing syndrome | 2015-08-31 | criteria provided, single submitter | clinical testing | The c.2308_2313delGGTAAGinsTG pathogenic mutation, located in coding exon 4 of the MSH6 gene, results from the deletion of 6 nucleotides and insertion of two nucleotides causing a translational frameshift with a predicted alternate stop codon. Since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). |
Invitae | RCV000704855 | SCV000833826 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2018-05-29 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). This variant has been reported in an individual affected with Lynch syndrome (PMID: 28874130, 10612827). The variant is also known as c.2308_2313delGGTAAGinsTG. ClinVar contains an entry for this variant (Variation ID: 220570). This variant is not present in population databases (ExAC no frequency). This sequence change deletes 5 nucleotides and inserts 1 nucleotide in exon 4 of the MSH6 mRNA (c.2308_2312delinsT), causing a frameshift at codon 770. This creates a premature translational stop signal (p.Gly770Cysfs*4) and is expected to result in an absent or disrupted protein product |
Myriad Genetics, |
RCV003477700 | SCV004222604 | pathogenic | Lynch syndrome 5 | 2023-08-16 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
Color Diagnostics, |
RCV000218163 | SCV004357643 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-04-26 | criteria provided, single submitter | clinical testing | This variant deletes 5 nucleotides and inserts 1 new nucleotide in exon 4 of the MSH6 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals affected with Lynch syndrome (PMID: 28874130), or endometrial cancer (PMID: 31068090). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MSH6 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |