Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Prevention |
RCV000679273 | SCV000805967 | uncertain significance | not provided | 2017-02-10 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001049050 | SCV001213084 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2021-11-20 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 560782). This variant has not been reported in the literature in individuals affected with MLH1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 723 of the MLH1 protein (p.Ala723Thr). 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 disruptive. 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 Diagnostics, |
RCV001178887 | SCV001343451 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-12-12 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV001178887 | SCV004053404 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-16 | criteria provided, single submitter | clinical testing | The p.A723T variant (also known as c.2167G>A), located in coding exon 19 of the MLH1 gene, results from a G to A substitution at nucleotide position 2167. The alanine at codon 723 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly 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. |
All of Us Research Program, |
RCV004004218 | SCV004843291 | uncertain significance | Lynch syndrome | 2023-08-25 | criteria provided, single submitter | clinical testing |