ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3679A>T (p.Ile1227Leu) (rs587779282)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000574037 SCV000662547 uncertain significance Hereditary cancer-predisposing syndrome 2017-03-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000574037 SCV000908429 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-12 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000625244 SCV000744301 uncertain significance Hereditary nonpolyposis colorectal cancer type 5 2017-05-31 criteria provided, single submitter clinical testing
GeneDx RCV000217680 SCV000279524 uncertain significance not provided 2015-10-28 criteria provided, single submitter clinical testing This variant is denoted MSH6 c.3679A>T at the cDNA level, p.Ile1227Leu (I1227L) at the protein level, and results in the change of an Isoleucine to a Leucine (ATA>TTA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH6 Ile1227Leu was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Isoleucine and Leucine share similar properties, this is considered a conservative amino acid substitution. MSH6 Ile1227Leu occurs at a position that is conserved across species and is located within domain V of the MutS domain (Terui 2013). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether MSH6 Ile1227Leu is pathogenic or benign. We consider it to be a variant of uncertain significance.
Genome Diagnostics Laboratory,VU University Medical Center Amsterdam RCV000625244 SCV000745654 uncertain significance Hereditary nonpolyposis colorectal cancer type 5 2017-05-21 no assertion criteria provided clinical testing
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000074913 SCV000108125 uncertain significance Lynch syndrome 2013-09-05 reviewed by expert panel research Insufficient evidence

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