ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3232T>C (p.Tyr1078His)

gnomAD frequency: 0.00001  dbSNP: rs367687901
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV004563003 SCV001518310 uncertain significance Familial adenomatous polyposis 1 2024-06-15 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 1078 of the APC protein (p.Tyr1078His). This variant is present in population databases (rs367687901, gnomAD 0.0009%). 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: 1026753). 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.
Ambry Genetics RCV002447378 SCV002611734 uncertain significance Hereditary cancer-predisposing syndrome 2024-01-05 criteria provided, single submitter clinical testing The p.Y1078H variant (also known as c.3232T>C), located in coding exon 15 of the APC gene, results from a T to C substitution at nucleotide position 3232. The tyrosine at codon 1078 is replaced by histidine, an amino acid with similar 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health RCV004005135 SCV004842897 uncertain significance Classic or attenuated familial adenomatous polyposis 2023-11-30 criteria provided, single submitter clinical testing

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