ClinVar Miner

Submissions for variant NM_000038.6(APC):c.5816A>T (p.Asp1939Val)

gnomAD frequency: 0.00001  dbSNP: rs754783550
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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 RCV000165007 SCV000215702 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-28 criteria provided, single submitter clinical testing The p.D1939V variant (also known as c.5816A>T), located in coding exon 15 of the APC gene, results from an A to T substitution at nucleotide position 5816. The aspartic acid at codon 1939 is replaced by valine, an amino acid with highly dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV003650421 SCV000552670 uncertain significance Familial adenomatous polyposis 1 2023-11-29 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 1939 of the APC protein (p.Asp1939Val). This variant is present in population databases (rs754783550, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 185564). 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 with a negative predictive value of 95%. 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 RCV000484552 SCV000567229 uncertain significance not provided 2019-09-27 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Color Diagnostics, LLC DBA Color Health RCV000165007 SCV000687048 uncertain significance Hereditary cancer-predisposing syndrome 2023-04-03 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with valine at codon 1939 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 APC-related disorders in the literature. This variant has been identified in 1/250146 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.
Counsyl RCV000463148 SCV000785437 uncertain significance Familial adenomatous polyposis 1 2017-08-09 criteria provided, single submitter clinical testing
Mendelics RCV000463148 SCV000838138 uncertain significance Familial adenomatous polyposis 1 2018-07-02 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV003316034 SCV004018025 uncertain significance Familial adenomatous polyposis 1 2023-02-16 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
Baylor Genetics RCV000463148 SCV004197475 uncertain significance Familial adenomatous polyposis 1 2023-10-30 criteria provided, single submitter clinical testing

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