ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3928A>T (p.Lys1310Ter)

dbSNP: rs2149902263
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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 RCV003337380 SCV002232857 pathogenic Familial adenomatous polyposis 1 2021-01-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys1310*) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1534 amino acid(s) of the APC protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with familial adenomatous polyposis (FAP) (PMID: 31360874). This variant is expected to disrupt the EB1 and HDLG binding sites, which mediate interactions with the cytoskeleton (PMID: 15311282, 17293347). While functional studies have not been performed to directly test the effect on APC protein function, this suggests that disruption of the C-terminal portion of the protein is functionally important. For these reasons, this variant has been classified as Pathogenic. A different truncation (p.Tyr2645Lysfs*14) that lies downstream of this variant has been determined to be pathogenic (PMID: 9824584, 1316610, 27081525, 8381579, 22135120, Invitae). This suggests that deletion of this region of the APC protein is causative of disease.
Ambry Genetics RCV002352643 SCV002621712 pathogenic Hereditary cancer-predisposing syndrome 2016-05-05 criteria provided, single submitter clinical testing The p.K1310* pathogenic mutation (also known as c.3928A>T), located in coding exon 15 of the APC gene, results from an A to T substitution at nucleotide position 3928. This changes the amino acid from a lysine to a stop codon within coding exon 15. Since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
Myriad Genetics, Inc. RCV003337380 SCV004042951 pathogenic Familial adenomatous polyposis 1 2023-05-09 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.

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