ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.2219T>G (p.Leu740Ter)

dbSNP: rs745483465
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Total submissions: 5
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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, Inc. 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, LLC DBA Color Health 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, National Institutes of Health 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.

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