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NM_000546.6(TP53):c.329G>C (p.Arg110Pro) AND Li-Fraumeni syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 29, 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:
RCV000231991.12

Allele description [Variation Report for NM_000546.6(TP53):c.329G>C (p.Arg110Pro)]

NM_000546.6(TP53):c.329G>C (p.Arg110Pro)

Gene:
TP53:tumor protein p53 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17p13.1
Genomic location:
Preferred name:
NM_000546.6(TP53):c.329G>C (p.Arg110Pro)
HGVS:
  • NC_000017.11:g.7676040C>G
  • NG_017013.2:g.16511G>C
  • NM_000546.6:c.329G>CMANE SELECT
  • NM_001126112.3:c.329G>C
  • NM_001126113.3:c.329G>C
  • NM_001126114.3:c.329G>C
  • NM_001126118.2:c.212G>C
  • NM_001276695.3:c.212G>C
  • NM_001276696.3:c.212G>C
  • NM_001276760.3:c.212G>C
  • NM_001276761.3:c.212G>C
  • NP_000537.3:p.Arg110Pro
  • NP_000537.3:p.Arg110Pro
  • NP_001119584.1:p.Arg110Pro
  • NP_001119585.1:p.Arg110Pro
  • NP_001119586.1:p.Arg110Pro
  • NP_001119590.1:p.Arg71Pro
  • NP_001263624.1:p.Arg71Pro
  • NP_001263625.1:p.Arg71Pro
  • NP_001263689.1:p.Arg71Pro
  • NP_001263690.1:p.Arg71Pro
  • LRG_321t1:c.329G>C
  • LRG_321:g.16511G>C
  • LRG_321p1:p.Arg110Pro
  • NC_000017.10:g.7579358C>G
  • NM_000546.4:c.329G>C
  • NM_000546.5:c.329G>C
  • P04637:p.Arg110Pro
Protein change:
R110P
Links:
UniProtKB: P04637#VAR_005862; dbSNP: rs11540654
NCBI 1000 Genomes Browser:
rs11540654
Molecular consequence:
  • NM_000546.6:c.329G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.329G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.3:c.329G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.3:c.329G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.2:c.212G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.3:c.212G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.3:c.212G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.3:c.212G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.3:c.212G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Li-Fraumeni syndrome (LFS)
Synonyms:
Sarcoma family syndrome of Li and Fraumeni
Identifiers:
MONDO: MONDO:0018875; MedGen: C0085390; OMIM: PS151623

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000285189Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Sep 29, 2023) 		germlineclinical testing

PubMed (11)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Gastric cancer in individuals with Li-Fraumeni syndrome.

Masciari S, Dewanwala A, Stoffel EM, Lauwers GY, Zheng H, Achatz MI, Riegert-Johnson D, Foretova L, Silva EM, Digianni L, Verselis SJ, Schneider K, Li FP, Fraumeni J, Garber JE, Syngal S.

Genet Med. 2011 Jul;13(7):651-7. doi: 10.1097/GIM.0b013e31821628b6.

PubMed [citation]
PMID:
21552135
PMCID:
PMC3595598

High frequency of germline TP53 mutations in a prospective adult-onset sarcoma cohort.

Mitchell G, Ballinger ML, Wong S, Hewitt C, James P, Young MA, Cipponi A, Pang T, Goode DL, Dobrovic A, Thomas DM; International Sarcoma Kindred Study..

PLoS One. 2013 Jul 22;8(7):e69026. doi: 10.1371/journal.pone.0069026. Print 2013.

PubMed [citation]
PMID:
23894400
PMCID:
PMC3718831
See all PubMed Citations (11)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000285189.10

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (11)

Description

This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 110 of the TP53 protein (p.Arg110Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with classical Li-Fraumeni syndrome (LFS) (PMID: 21552135, 23894400, 29070607; Invitae). ClinVar contains an entry for this variant (Variation ID: 233627). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is expected to disrupt TP53 function. Experimental studies have shown that this missense change affects TP53 function (PMID: 12826609, 23897043, 24076587). This variant disrupts the p.Arg110 amino acid residue in TP53. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16778209, 21445056, 24076587; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Sep 29, 2024