ClinVar Miner

Submissions for variant NM_000038.6(APC):c.876G>C (p.Leu292Phe)

dbSNP: rs760059672
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000410953 SCV000489556 uncertain significance Familial adenomatous polyposis 1 2016-10-21 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000410953 SCV000647784 uncertain significance Familial adenomatous polyposis 1 2024-08-22 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 292 of the APC protein (p.Leu292Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with non-medullary thyroid cancer (PMID: 26530882). ClinVar contains an entry for this variant (Variation ID: 372035). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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.
Color Diagnostics, LLC DBA Color Health RCV001178393 SCV001342831 uncertain significance Hereditary cancer-predisposing syndrome 2024-01-31 criteria provided, single submitter clinical testing This missense variant replaces leucine with phenylalanine at codon 292 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 performed for this variant. This variant has been reported in two related individuals affected with familial non-medullary thyroid cancer (PMID: 26530882). This variant has not been identified 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.
Ambry Genetics RCV001178393 SCV002687238 uncertain significance Hereditary cancer-predisposing syndrome 2024-10-04 criteria provided, single submitter clinical testing The p.L292F variant (also known as c.876G>C), located in coding exon 8 of the APC gene, results from a G to C substitution at nucleotide position 876. The leucine at codon 292 is replaced by phenylalanine, an amino acid with highly similar properties. This alteration was detected in two non-medullary thyroid cancer patients from the same family (Yu Y et al. Sci Rep, 2015 Nov;5:16129). This amino acid position is not 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.
Myriad Genetics, Inc. RCV000410953 SCV004018108 uncertain significance Familial adenomatous polyposis 1 2023-02-14 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.
All of Us Research Program, National Institutes of Health RCV004804991 SCV005428503 uncertain significance Classic or attenuated familial adenomatous polyposis 2024-02-22 criteria provided, single submitter clinical testing This missense variant replaces leucine with phenylalanine at codon 292 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in an individual affected with familial non-medullary thyroid cancer (PMID: 26530882). This variant has not been identified 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.
3DMed Clinical Laboratory Inc RCV000677755 SCV000803911 uncertain significance Gastrointestinal stromal tumor 2017-07-25 no assertion criteria provided clinical testing

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