ClinVar Miner

Submissions for variant NM_000038.6(APC):c.4451A>T (p.Asp1484Val)

gnomAD frequency: 0.00002  dbSNP: rs895694427
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV004564450 SCV000835982 uncertain significance Familial adenomatous polyposis 1 2022-03-29 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 582757). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 1484 of the APC protein (p.Asp1484Val).
Ambry Genetics RCV002332513 SCV002637135 uncertain significance Hereditary cancer-predisposing syndrome 2024-11-15 criteria provided, single submitter clinical testing The p.D1484V variant (also known as c.4451A>T), located in coding exon 15 of the APC gene, results from an A to T substitution at nucleotide position 4451. The aspartic acid at codon 1484 is replaced by valine, an amino acid with highly dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Missense alterations in APC are not a common cause of disease (Spier I et al. Genet Med. 2024 Feb;26(2):100992). Based on the available evidence, the clinical significance of this variant remains unclear.
GeneDx RCV003329335 SCV004036277 uncertain significance not provided 2023-03-21 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 18199528)
All of Us Research Program, National Institutes of Health RCV003999778 SCV004842107 uncertain significance Classic or attenuated familial adenomatous polyposis 2023-12-13 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with valine at codon 1484 of the APC protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, 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 1/31400 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.

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