ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3295A>G (p.Ile1099Val) (rs1064795895)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000485734 SCV000572127 uncertain significance not provided 2016-10-27 criteria provided, single submitter clinical testing This variant is denoted MSH6 c.3295A>G at the cDNA level, p.Ile1099Val (I1099V) at the protein level, and results in the change of an Isoleucine to a Valine (ATT>GTT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH6 Ile1099Val 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 Valine share similar properties, this is considered a conservative amino acid substitution. MSH6 Ile1099Val occurs at a position where amino acids with properties similar to Isoleucine are tolerated across species and is located in domain V of the MutS domain (Terui 2013). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether MSH6 Ile1099Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000573659 SCV000669917 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence

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