Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV004048467 | SCV002610452 | uncertain significance | not specified | 2024-04-20 | criteria provided, single submitter | clinical testing | The c.3148G>A (p.V1050I) alteration is located in exon 2 (coding exon 1) of the MLH3 gene. This alteration results from a G to A substitution at nucleotide position 3148, causing the valine (V) at amino acid position 1050 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV003505207 | SCV004363782 | uncertain significance | Colorectal cancer, hereditary nonpolyposis, type 7 | 2022-11-30 | criteria provided, single submitter | clinical testing | 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. 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. This variant has not been reported in the literature in individuals affected with MLH3-related conditions. This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1050 of the MLH3 protein (p.Val1050Ile). This variant is not present in population databases (gnomAD no frequency). |