ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.3439G>A (p.Ala1147Thr)

gnomAD frequency: 0.00001  dbSNP: rs770054790
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000168374 SCV000219065 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2024-01-02 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1147 of the MSH6 protein (p.Ala1147Thr). This variant is present in population databases (rs770054790, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 188347). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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.
Ambry Genetics RCV000565176 SCV000662480 uncertain significance Hereditary cancer-predisposing syndrome 2024-02-14 criteria provided, single submitter clinical testing The p.A1147T variant (also known as c.3439G>A) is located in coding exon 6 of the MSH6 gene. The alanine at codon 1147 is replaced by threonine, an amino acid with similar properties. This change occurs in the first base pair of coding exon 6. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV003320590 SCV004024804 uncertain significance not specified 2023-08-15 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003995624 SCV004815951 uncertain significance Lynch syndrome 2023-02-24 criteria provided, single submitter clinical testing This missense variant replaces alanine with threonine at codon 1147 of the MSH6 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 2/251432 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.