Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene label mismatch: APC vs undefined
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000038.6(APC):c.4139C>T (p.Thr1380Ile)

CA10578369

233890 (ClinVar)

Gene: APC
Condition: familial adenomatous polyposis 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 25434977-5e37-4bdd-9463-8ddcb380e55b
Approved on: 2025-05-16
Published on: 2025-05-16

HGVS expressions

NM_000038.6:c.4139C>T
NM_000038.6(APC):c.4139C>T (p.Thr1380Ile)
NC_000005.10:g.112839733C>T
CM000667.2:g.112839733C>T
NC_000005.9:g.112175430C>T
CM000667.1:g.112175430C>T
NC_000005.8:g.112203329C>T
NG_008481.4:g.152213C>T
ENST00000502371.3:c.3804C>T
ENST00000504915.3:c.4193C>T
ENST00000505350.2:c.*4145C>T
ENST00000507379.6:c.4085C>T
ENST00000509732.6:c.4139C>T
ENST00000512211.7:c.4139C>T
ENST00000257430.9:c.4139C>T
ENST00000257430.8:c.4139C>T
ENST00000502371.2:c.2492C>T
ENST00000508376.6:c.4139C>T
ENST00000508624.5:c.*3461C>T
ENST00000520401.1:c.230+10761C>T
NM_000038.5:c.4139C>T
NM_001127510.2:c.4139C>T
NM_001127511.2:c.4085C>T
NM_001354895.1:c.4139C>T
NM_001354896.1:c.4193C>T
NM_001354897.1:c.4169C>T
NM_001354898.1:c.4064C>T
NM_001354899.1:c.4055C>T
NM_001354900.1:c.4016C>T
NM_001354901.1:c.3962C>T
NM_001354902.1:c.3866C>T
NM_001354903.1:c.3836C>T
NM_001354904.1:c.3761C>T
NM_001354905.1:c.3659C>T
NM_001354906.1:c.3290C>T
NM_001127510.3:c.4139C>T
NM_001127511.3:c.4085C>T
NM_001354895.2:c.4139C>T
NM_001354896.2:c.4193C>T
NM_001354897.2:c.4169C>T
NM_001354898.2:c.4064C>T
NM_001354899.2:c.4055C>T
NM_001354900.2:c.4016C>T
NM_001354901.2:c.3962C>T
NM_001354902.2:c.3866C>T
NM_001354903.2:c.3836C>T
NM_001354904.2:c.3761C>T
NM_001354905.2:c.3659C>T
NM_001354906.2:c.3290C>T
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Uncertain Significance

Met criteria codes 3
BP1 PS4_Moderate PM2_Supporting

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for APC Version 2.1.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP
The NM_000038.6(APC):c.4139C>T variant in APC is a missense variant predicted to cause substitution of Threonine by Isoleucine at amino acid position 1380 (p.Thr1380Ile). This variant has been reported in 6 probands meeting phenotypic criteria, resulting in a total phenotype score of 3 points (PS4_Moderate [Ambry Genetics, Invitae]). The variant has been reported in 2 additional probands with a colorectal cancer/polyposis associated phenotype not meeting phenotypic criteria and one unaffected individual with a positive family history for colorectal polyposis (Invitae). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). APC, in which the variant was identified, is defined by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP (HCCP VCEP) as a gene for which primarily truncating variants are known to cause disease (BP1). In summary, this variant is a VUS for autosomal-dominant inherited FAP based on the ACMG/AMP criteria applied, as specified by the HCCP VCEP: criteria BP1, PS4_Moderate, PM2_Supporting applied (VCEP specifications v2.0.3; date of approval 7/24/2023).
Met criteria codes
BP1
APC, in which the variant was identified, is defined by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP (HCCP VCEP) as a gene for which primarily truncating variants are known to cause disease (BP1).
PS4_Moderate
This variant has been reported in 6 probands meeting phenotypic criteria, resulting in a total phenotype score of 3 points (PS4_Moderate [Ambry Genetics, Invitae]). The variant has been reported in 2 additional probands with a colorectal cancer/polyposis associated phenotype not meeting phenotypic criteria and one unaffected individual with a positive family history for colorectal polyposis (Invitae).
PM2_Supporting
This variant is absent from gnomAD v2.1.1 (PM2_Supporting).
Curation History
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