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NM_000546.6(TP53):c.331C>A (p.Leu111Met) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 26, 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:
RCV003307811.2

Allele description [Variation Report for NM_000546.6(TP53):c.331C>A (p.Leu111Met)]

NM_000546.6(TP53):c.331C>A (p.Leu111Met)

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.331C>A (p.Leu111Met)
HGVS:
  • NC_000017.11:g.7676038G>T
  • NG_017013.2:g.16513C>A
  • NM_000546.4:c.331C>A
  • NM_000546.6:c.331C>AMANE SELECT
  • NM_001126112.3:c.331C>A
  • NM_001126113.3:c.331C>A
  • NM_001126114.3:c.331C>A
  • NM_001126118.2:c.214C>A
  • NM_001276695.3:c.214C>A
  • NM_001276696.3:c.214C>A
  • NM_001276760.3:c.214C>A
  • NM_001276761.3:c.214C>A
  • NP_000537.3:p.Leu111Met
  • NP_001119584.1:p.Leu111Met
  • NP_001119585.1:p.Leu111Met
  • NP_001119586.1:p.Leu111Met
  • NP_001119590.1:p.Leu72Met
  • NP_001263624.1:p.Leu72Met
  • NP_001263625.1:p.Leu72Met
  • NP_001263689.1:p.Leu72Met
  • NP_001263690.1:p.Leu72Met
  • LRG_321t1:c.331C>A
  • LRG_321:g.16513C>A
  • NC_000017.10:g.7579356G>T
  • NM_000546.5:c.331C>A
Protein change:
L111M
Links:
dbSNP: rs1403707528
NCBI 1000 Genomes Browser:
rs1403707528
Molecular consequence:
  • NM_000546.6:c.331C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.331C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.3:c.331C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.3:c.331C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.2:c.214C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.3:c.214C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.3:c.214C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.3:c.214C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.3:c.214C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003998797Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(May 26, 2023) 		germlineclinical testing

Citation Link

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Summary from all submissions

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

Details of each submission

From Ambry Genetics, SCV003998797.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The p.L111M variant (also known as c.331C>A), located in coding exon 3 of the TP53 gene, results from a C to A substitution at nucleotide position 331. The leucine at codon 111 is replaced by methionine, an amino acid with highly similar properties. This variant is in the DNA binding domain of the TP53 protein and is reported to have partially functional transactivation in yeast based assays (Kato S et al. Proc. Natl. Acad. Sci. USA. 2003 Jul;100:8424-9). Studies conducted in human cell lines indicate this alteration is proficient at growth suppression and has no dominant negative effect (Kotler E et al. Mol.Cell. 2018 Jul;71:178-190.e8; Giacomelli AO et al. Nat. Genet. 2018 Oct;50:1381-1387). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

Last Updated: Nov 10, 2024