ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.2562G>T (p.Lys854Asn)

gnomAD frequency: 0.00005  dbSNP: rs759048538
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina 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, 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, Medical Diagnostic Laboratories, L.L.C. 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, National Institutes of Health 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.