ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6011_6012insTT (p.Ser2005fs)

dbSNP: rs1561604514
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV003336149 SCV000826203 pathogenic Familial adenomatous polyposis 1 2022-12-14 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 575384). This premature translational stop signal has been observed in individual(s) with APC-related conditions (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser2005Tyrfs*40) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 839 amino acid(s) of the APC protein.
Ambry Genetics RCV002352167 SCV002655139 pathogenic Hereditary cancer-predisposing syndrome 2022-10-24 criteria provided, single submitter clinical testing The c.6011_6012insTT pathogenic mutation, located in coding exon 15 of the APC gene, results from an insertion of two nucleotides at position 6011, causing a translational frameshift with a predicted alternate stop codon (p.S2005Yfs*40). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Myriad Genetics, Inc. RCV003336149 SCV004044037 pathogenic Familial adenomatous polyposis 1 2023-05-15 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

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