Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001149363 | SCV001310309 | uncertain significance | Colorectal cancer, hereditary nonpolyposis, type 2 | 2017-04-28 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
| Invitae | RCV003593923 | SCV004369914 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-07-07 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MLH1 protein function. ClinVar contains an entry for this variant (Variation ID: 183068). This variant has not been reported in the literature in individuals affected with MLH1-related conditions. This variant is present in population databases (rs730882127, gnomAD 0.03%). This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 31 of the MLH1 protein (p.Ala31Gly). |
| Center for Genomic Medicine, |
RCV001149363 | SCV004807214 | uncertain significance | Colorectal cancer, hereditary nonpolyposis, type 2 | 2024-03-26 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV000161932 | SCV004835233 | uncertain significance | Lynch syndrome | 2024-01-11 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with glycine at codon 31 of the MLH1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 MLH1-related disorders in the literature. This variant has been identified in 22/282508 chromosomes 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. |
| Invitae | RCV000161932 | SCV000211916 | uncertain significance | Lynch syndrome | 2015-02-18 | no assertion criteria provided | clinical testing |