Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001015143 | SCV001175947 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-30 | criteria provided, single submitter | clinical testing | The p.T772A variant (also known as c.2314A>G), located in coding exon 14 of the MSH2 gene, results from an A to G substitution at nucleotide position 2314. The threonine at codon 772 is replaced by alanine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV001202641 | SCV001373763 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2021-05-19 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. This variant has not been reported in the literature in individuals with MSH2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with alanine at codon 772 of the MSH2 protein (p.Thr772Ala). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and alanine. |
Sema4, |
RCV001015143 | SCV002534466 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-11 | criteria provided, single submitter | curation | |
Color Diagnostics, |
RCV001015143 | SCV004356736 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-23 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with alanine at codon 772 of the MSH2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |