Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000276074 | SCV000430972 | uncertain significance | Lynch syndrome | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000630372 | SCV000751328 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2024-02-01 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV002256216 | SCV002535753 | likely benign | Hereditary cancer-predisposing syndrome | 2021-01-31 | criteria provided, single submitter | curation | |
Ambry Genetics | RCV002256216 | SCV002740229 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-04-21 | criteria provided, single submitter | clinical testing | The p.K854N variant (also known as c.2562G>T), located in coding exon 4 of the MSH6 gene, results from a G to T substitution at nucleotide position 2562. The lysine at codon 854 is replaced by asparagine, an amino acid with similar properties. In a study of whole-exome sequencing in patients with features of Cowden syndrome (CS) or Bannayan-Riley-Ruvalcaba syndrome (BRRS) and negative PTEN testing, this alteration was identified in 0/87 patients with CS or BRRS and 1/3476 patients from The Cancer Genome Atlas (TCGA) (Yehia L et al. PLoS Genet, 2018 04;14:e1007352). This amino acid position is highly 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. |
Institute for Biomarker Research, |
RCV002256216 | SCV004014978 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-05 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV003463784 | SCV004197565 | uncertain significance | Endometrial carcinoma | 2023-10-30 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV000276074 | SCV004842660 | uncertain significance | Lynch syndrome | 2023-12-13 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with asparagine at codon 854 of the MSH6 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 been reported in an individual affected with kidney cancer (PMID: 29684080). This variant has been identified in 22/280654 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. |