Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000235367 | SCV000292975 | uncertain significance | not provided | 2016-02-25 | criteria provided, single submitter | clinical testing | This variant is denoted MSH2 c.38G>A at the cDNA level, p.Ser13Asn (S13N) at the protein level, and results in the change of a Serine to an Asparagine (AGC>AAC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH2 Ser13Asn 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 Serine and Asparagine share similar properties, this is considered a conservative amino acid substitution. MSH2 Ser13Asn occurs at a position that is not conserved and is located within the mismatch binding 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 Ser13Asn is pathogenic or benign. We consider it to be a variant of uncertain significance. |
Ambry Genetics | RCV000572196 | SCV000676072 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-08-30 | criteria provided, single submitter | clinical testing | The p.S13N variant (also known as c.38G>A), located in coding exon 1 of the MSH2 gene, results from a G to A substitution at nucleotide position 38. The serine at codon 13 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. In addition, this alteration is predicted to be benign by MAPP-MMR in silico analyses (Chao EC et al. Hum. Mutat. 2008 Jun;29:852-60). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV000688689 | SCV000816311 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2019-11-19 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with asparagine at codon 13 of the MSH2 protein (p.Ser13Asn). The serine residue is weakly conserved and there is a small physicochemical difference between serine and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MSH2-related disease. ClinVar contains an entry for this variant (Variation ID: 245828). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Color | RCV000572196 | SCV001356786 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-12 | criteria provided, single submitter | clinical testing |