ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.2341C>A (p.Pro781Thr) (rs587779235)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160680 SCV000211295 uncertain significance not specified 2017-03-10 criteria provided, single submitter clinical testing This variant is denoted MSH6 c.2341C>A at the cDNA level, p.Pro781Thr (P781T) at the protein level, and results in the change of a Proline to a Threonine (CCA>ACA) in exon 4. This variant has not, to our knowledge, been published in the literature as either a mutation or a benign polymorphism. MSH6 Pro781Thr was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Proline and Threonine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution and is likely to affect protein integrity. MSH6 Pro781Thr alters a position that is highly conserved across species and is located in the Domain III 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 information, it is unclear whether MSH6 Pro781Thr is a pathogenic mutation or a benign variant. The variant is found in ENDOM-HEREDIC panel(s).
Ambry Genetics RCV000491573 SCV000580323 uncertain significance Hereditary cancer-predisposing syndrome 2016-02-17 criteria provided, single submitter clinical testing Insufficient or conflicting evidence;In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000659892 SCV000781789 uncertain significance Hereditary nonpolyposis colorectal cancer type 5 2016-11-01 criteria provided, single submitter clinical testing

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