Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000223630 | SCV000275942 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-12 | criteria provided, single submitter | clinical testing | The p.N306I variant (also known as c.917A>T), located in coding exon 11 of the MLH1 gene, results from an A to T substitution at nucleotide position 917. The asparagine at codon 306 is replaced by isoleucine, an amino acid with dissimilar properties. This alteration has been reported in a cohort of high risk breast and ovarian cancer patients (Castéra L et al, Eur. J. Hum. Genet. 2014 Nov; 22(11):1305-1). 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. |
Gene |
RCV000485727 | SCV000565151 | uncertain significance | not provided | 2021-12-06 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Identified in individuals with a personal and/or family history of breast and/or ovarian cancer (Castera 2014); This variant is associated with the following publications: (PMID: 22753075, 24549055) |
Color Diagnostics, |
RCV000223630 | SCV000904892 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-07-30 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000818768 | SCV000959400 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-12-11 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 306 of the MLH1 protein (p.Asn306Ile). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with hereditary breast and/or ovarian cancer (PMID: 24549055). ClinVar contains an entry for this variant (Variation ID: 231940). 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 with a positive predictive value of 95%. 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. |
All of Us Research Program, |
RCV003997935 | SCV004840919 | uncertain significance | Lynch syndrome | 2023-05-31 | criteria provided, single submitter | clinical testing |