ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6639G>A (p.Met2213Ile) (rs35540155)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130211 SCV000185049 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-29 criteria provided, single submitter clinical testing The p.M2213I variant (also known as c.6639G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 6639. The methionine at codon 2213 is replaced by isoleucine, an amino acid with highly similar properties. This alteration was identified in a cohort of 1260 individuals undergoing panel testing for Lynch syndrome due to having a diagnosis of a Lynch-associated cancer and/or polyps (Yurgelun MB et al. Gastroenterology. 2015 Sep;149:604-13.e20). This alteration was also identified in a cohort of 100 individuals from Qatar undergoing whole exome sequencing (Rodriguez-Flores JL et al. Hum. Mutat. 2014 Jan;35:105-16). 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.
Counsyl RCV000409211 SCV000488876 uncertain significance Familial adenomatous polyposis 1 2016-07-18 criteria provided, single submitter clinical testing
Invitae RCV000409211 SCV000552646 benign Familial adenomatous polyposis 1 2020-12-04 criteria provided, single submitter clinical testing
GeneDx RCV000484737 SCV000566001 likely benign not provided 2020-12-15 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25980754, 24123366, 21153778, 31159747)
GeneKor MSA RCV000130211 SCV000821822 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765788 SCV000897177 uncertain significance Desmoid disease, hereditary; Carcinoma of colon; Familial adenomatous polyposis 1; Neoplasm of stomach; Hepatocellular carcinoma 2018-10-31 criteria provided, single submitter clinical testing
Color Health, Inc RCV000130211 SCV000910766 likely benign Hereditary cancer-predisposing syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001157265 SCV001318816 uncertain significance APC-Associated Polyposis Disorders 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

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