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NM_000038.6(APC):c.1644G>C (p.Leu548Phe) AND Familial adenomatous polyposis 1

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jun 5, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003770958.1

Allele description [Variation Report for NM_000038.6(APC):c.1644G>C (p.Leu548Phe)]

NM_000038.6(APC):c.1644G>C (p.Leu548Phe)

Gene:
APC:APC regulator of WNT signaling pathway [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q22.2
Genomic location:
Preferred name:
NM_000038.6(APC):c.1644G>C (p.Leu548Phe)
HGVS:
  • NC_000005.10:g.112828873G>C
  • NG_008481.4:g.141353G>C
  • NM_000038.6:c.1644G>CMANE SELECT
  • NM_001127510.3:c.1644G>C
  • NM_001127511.3:c.1590G>C
  • NM_001354895.2:c.1644G>C
  • NM_001354896.2:c.1698G>C
  • NM_001354897.2:c.1674G>C
  • NM_001354898.2:c.1569G>C
  • NM_001354899.2:c.1560G>C
  • NM_001354900.2:c.1521G>C
  • NM_001354901.2:c.1467G>C
  • NM_001354902.2:c.1371G>C
  • NM_001354903.2:c.1341G>C
  • NM_001354904.2:c.1266G>C
  • NM_001354905.2:c.1164G>C
  • NM_001354906.2:c.795G>C
  • NP_000029.2:p.Leu548Phe
  • NP_001120982.1:p.Leu548Phe
  • NP_001120983.2:p.Leu530Phe
  • NP_001341824.1:p.Leu548Phe
  • NP_001341825.1:p.Leu566Phe
  • NP_001341826.1:p.Leu558Phe
  • NP_001341827.1:p.Leu523Phe
  • NP_001341828.1:p.Leu520Phe
  • NP_001341829.1:p.Leu507Phe
  • NP_001341830.1:p.Leu489Phe
  • NP_001341831.1:p.Leu457Phe
  • NP_001341832.1:p.Leu447Phe
  • NP_001341833.1:p.Leu422Phe
  • NP_001341834.1:p.Leu388Phe
  • NP_001341835.1:p.Leu265Phe
  • LRG_130:g.141353G>C
  • NC_000005.9:g.112164570G>C
Protein change:
L265F
Links:
dbSNP: rs1764009998
NCBI 1000 Genomes Browser:
rs1764009998
Molecular consequence:
  • NM_000038.6:c.1644G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127510.3:c.1644G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127511.3:c.1590G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354895.2:c.1644G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354896.2:c.1698G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354897.2:c.1674G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354898.2:c.1569G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354899.2:c.1560G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354900.2:c.1521G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354901.2:c.1467G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354902.2:c.1371G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354903.2:c.1341G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354904.2:c.1266G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354905.2:c.1164G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354906.2:c.795G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Familial adenomatous polyposis 1 (FAP1)
Synonyms:
POLYPOSIS, ADENOMATOUS INTESTINAL; FAMILIAL ADENOMATOUS POLYPOSIS 1, ATTENUATED; APC-Associated Polyposis Conditions
Identifiers:
MONDO: MONDO:0021056; MedGen: C2713442; OMIM: 175100

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001539974Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Jun 5, 2023)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001539974.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

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. ClinVar contains an entry for this variant (Variation ID: 1041944). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 548 of the APC protein (p.Leu548Phe). 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 15, 2024