Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000479663 | SCV000567966 | uncertain significance | not provided | 2015-09-16 | criteria provided, single submitter | clinical testing | This variant is denoted MSH2 c.959C>A at the cDNA level, p.Thr320Asn (T320N) at the protein level, and results in the change of a Threonine to an Asparagine (ACC>AAC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH2 Thr320Asn 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 Threonine and Asparagine share similar properties, this is considered a conservative amino acid substitution. MSH2 Thr320Asn occurs at a position that is not conserved and is located in the Lever domain (Lutzen 2008). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether MSH2 Thr320Asn is pathogenic or benign. We consider it to be a variant of uncertain significance. |