ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1313CTC[1] (p.Pro439del) (rs587779082)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000411959 SCV000488947 uncertain significance Lynch syndrome I 2016-07-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV000491828 SCV000580573 likely pathogenic Hereditary cancer-predisposing syndrome 2020-02-06 criteria provided, single submitter clinical testing The c.1316_1318delCTC variant (also known as p.P439del) is located in coding exon 8 of the MSH2 gene. This variant results from an in-frame CTC deletion of nucleotide positions 1316 through 1318. This variant was detected in individuals who either met Bethesda/Amsterdam criteria for HNPCC/Lynch syndrome and had colorectal tumors that demonstrated high microsatellite instability (MSI-H) and/or absent MSH2 protein expression on immunohistochemistry (IHC) (Nagasaka T, et al. Cancer Res. 2010;70(8):3098-108, Jeong SY, et al. Dis. Colon Rectum 2003;46(8):1069-77; Ambry internal data). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species.​ In addition, this alteration is predicted to be deleterious<span style="color:#FF0000"> by in silico analysis (Choi Y et al., PLoS ONE 2012; 7(10):e46688). Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Invitae RCV000528474 SCV000625249 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-11-22 criteria provided, single submitter clinical testing This variant, c.1316_1318delCTC, results in the deletion of 1 amino acid of the MSH2 protein (p.Pro439del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals and families affected with Lynch syndrome (PMID: 15365995, 20388775). This variant is also known as c.1316_1318delCCT (p.Leu440del) in the literature. ClinVar contains an entry for this variant (Variation ID: 90623). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acid is currently unknown. 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.
Color Health, Inc RCV000491828 SCV000904680 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-19 criteria provided, single submitter clinical testing
Institute of Human Genetics,University of Wuerzburg RCV000850309 SCV000992484 likely pathogenic Neoplasm of the rectum no assertion criteria provided clinical testing

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