ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.604C>G (p.Pro202Ala) (rs1064794301)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000487037 SCV000568721 uncertain significance not provided 2016-08-31 criteria provided, single submitter clinical testing This variant is denoted MSH6 c.604C>G at the cDNA level, p.Pro202Ala (P202A) at the protein level, and results in the change of a Proline to an Alanine (CCA>GCA). This variant was observed in an early onset colorectal cancer patient with loss of MSH6 protein staining by immunohistochemistry (Giraldez 2010). MSH6 Pro202Ala 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 Proline and Alanine differ in some properties, this is considered a semi-conservative amino acid substitution. MSH6 Pro202Ala occurs at a position that is not conserved and is not located in a known functional domain (Kariola 2002). 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 Pro202Ala is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000565541 SCV000662500 uncertain significance Hereditary cancer-predisposing syndrome 2016-08-09 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence

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