ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7877C>T (p.Thr2626Ile)

gnomAD frequency: 0.00001  dbSNP: rs730881268
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159579 SCV000209555 uncertain significance not provided 2018-09-07 criteria provided, single submitter clinical testing This variant is denoted APC c.7877C>T at the cDNA level, p.Thr2626Ile (T2626I) at the protein level, and results in the change of a Threonine to an Isoleucine (ACT>ATT). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. APC Thr2626Ile was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the EB1 binding domain (Azzopardi 2008). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether APC Thr2626Ile is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color Diagnostics, LLC DBA Color Health RCV000583290 SCV000687148 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-19 criteria provided, single submitter clinical testing This missense variant replaces threonine with isoleucine at codon 2626 of the APC 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 2/250178 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.
Invitae RCV003534416 SCV000945262 uncertain significance Familial adenomatous polyposis 1 2023-09-01 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt APC protein function. ClinVar contains an entry for this variant (Variation ID: 181827). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is present in population databases (rs730881268, gnomAD 0.002%). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 2626 of the APC protein (p.Thr2626Ile).
Ambry Genetics RCV000583290 SCV002678160 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-29 criteria provided, single submitter clinical testing The p.T2626I variant (also known as c.7877C>T), located in coding exon 15 of the APC gene, results from a C to T substitution at nucleotide position 7877. The threonine at codon 2626 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is conserved. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003230419 SCV003928828 uncertain significance not specified 2023-04-14 criteria provided, single submitter clinical testing
Baylor Genetics RCV002515105 SCV004205382 uncertain significance Familial adenomatous polyposis 1 2023-06-09 criteria provided, single submitter clinical testing

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