Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001014787 | SCV001175542 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-08-23 | criteria provided, single submitter | clinical testing | The p.L740* pathogenic mutation (also known as c.2219T>G), located in coding exon 4 of the MSH6 gene, results from a T to G substitution at nucleotide position 2219. This changes the amino acid from a leucine to a stop codon within coding exon 4. 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 | RCV001222639 | SCV001394749 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-08-29 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 820891). This premature translational stop signal has been observed in individual(s) with MSH6-related conditions (PMID: 21520333). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Leu740*) 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). |
Myriad Genetics, |
RCV003455088 | SCV004185638 | pathogenic | Lynch syndrome 5 | 2023-08-16 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |
Color Diagnostics, |
RCV001014787 | SCV004357640 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-04-27 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 4 of the MSH6 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in an individual affected with Lynch syndrome (PMID: 32635641). This variant has been identified in 1/250898 chromosomes 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. |
All of Us Research Program, |
RCV004004537 | SCV004834044 | pathogenic | Lynch syndrome | 2023-07-19 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 4 of the MSH6 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in an individual affected with Lynch syndrome (PMID: 32635641). This variant has been identified in 1/250898 chromosomes 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. |