ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1828A>G (p.Lys610Glu) (rs199700509)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000168273 SCV000218945 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2020-10-01 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamic acid at codon 610 of the PMS2 protein (p.Lys610Glu). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is present in population databases (rs199700509, ExAC 0.004%). This variant has been reported in an individual affected with lung cancer (PMID: 26689913). ClinVar contains an entry for this variant (Variation ID: 188287). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Benign; Align-GVGD: Class C0. The glutamic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
GeneDx RCV000486825 SCV000567198 uncertain significance not provided 2021-07-08 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 does not alter protein structure/function; Observed in an individual with lung cancer (Lu 2015); This variant is associated with the following publications: (PMID: 27535533, 26689913)
Ambry Genetics RCV000574365 SCV000663448 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-26 criteria provided, single submitter clinical testing The p.K610E variant (also known as c.1828A>G), located in coding exon 11 of the PMS2 gene, results from an A to G substitution at nucleotide position 1828. The lysine at codon 610 is replaced by glutamic acid, an amino acid with similar properties. This alteration has been reported in a lung cancer patient from a cohort of 4034 cancer cases from The Cancer Genome Atlas (Lu C et al. Nat Commun, 2015 Dec;6:10086). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Health, Inc RCV000574365 SCV000902934 likely benign Hereditary cancer-predisposing syndrome 2015-07-15 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000486825 SCV001155028 uncertain significance not provided 2019-05-01 criteria provided, single submitter clinical testing

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