Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Mendelics | RCV000708824 | SCV000837811 | uncertain significance | Lynch syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001052926 | SCV001217162 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-10-20 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 22 of the MSH2 protein (p.Phe22Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Lynch syndrome (PMID: 31391288). ClinVar contains an entry for this variant (Variation ID: 584604). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 33357406) indicates that this missense variant is not expected to disrupt MSH2 function with a negative predictive value of 80%. 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. |
Ambry Genetics | RCV002360839 | SCV002659265 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-03-29 | criteria provided, single submitter | clinical testing | The p.F22I variant (also known as c.64T>A), located in coding exon 1 of the MSH2 gene, results from a T to A substitution at nucleotide position 64. The phenylalanine at codon 22 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |