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NM_000546.6(TP53):c.365T>C (p.Val122Ala) AND Li-Fraumeni syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 13, 2021
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:
RCV001979494.4

Allele description [Variation Report for NM_000546.6(TP53):c.365T>C (p.Val122Ala)]

NM_000546.6(TP53):c.365T>C (p.Val122Ala)

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.365T>C (p.Val122Ala)
HGVS:
  • NC_000017.11:g.7676004A>G
  • NG_017013.2:g.16547T>C
  • NM_000546.6:c.365T>CMANE SELECT
  • NM_001126112.3:c.365T>C
  • NM_001126113.3:c.365T>C
  • NM_001126114.3:c.365T>C
  • NM_001126118.2:c.248T>C
  • NM_001276695.3:c.248T>C
  • NM_001276696.3:c.248T>C
  • NM_001276760.3:c.248T>C
  • NM_001276761.3:c.248T>C
  • NP_000537.3:p.Val122Ala
  • NP_001119584.1:p.Val122Ala
  • NP_001119585.1:p.Val122Ala
  • NP_001119586.1:p.Val122Ala
  • NP_001119590.1:p.Val83Ala
  • NP_001263624.1:p.Val83Ala
  • NP_001263625.1:p.Val83Ala
  • NP_001263689.1:p.Val83Ala
  • NP_001263690.1:p.Val83Ala
  • LRG_321:g.16547T>C
  • NC_000017.10:g.7579322A>G
  • NM_000546.4:c.365T>C
Protein change:
V122A
Links:
dbSNP: rs2151038394
NCBI 1000 Genomes Browser:
rs2151038394
Molecular consequence:
  • NM_000546.6:c.365T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.365T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.3:c.365T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.3:c.365T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.2:c.248T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.3:c.248T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.3:c.248T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.3:c.248T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.3:c.248T>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
SCV002256058Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Oct 13, 2021) 		germlineclinical testing

PubMed (4)
[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

Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis.

Kato S, Han SY, Liu W, Otsuka K, Shibata H, Kanamaru R, Ishioka C.

Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8424-9. Epub 2003 Jun 25.

PubMed [citation]
PMID:
12826609
PMCID:
PMC166245

A Systematic p53 Mutation Library Links Differential Functional Impact to Cancer Mutation Pattern and Evolutionary Conservation.

Kotler E, Shani O, Goldfeld G, Lotan-Pompan M, Tarcic O, Gershoni A, Hopf TA, Marks DS, Oren M, Segal E.

Mol Cell. 2018 Jul 5;71(1):178-190.e8. doi: 10.1016/j.molcel.2018.06.012. Erratum in: Mol Cell. 2018 Sep 6;71(5):873. doi: 10.1016/j.molcel.2018.08.013.

PubMed [citation]
PMID:
29979965
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002256058.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on TP53 function (PMID: 12826609, 29979965, 30224644). This variant has not been reported in the literature in individuals affected with TP53-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with alanine at codon 122 of the TP53 protein (p.Val122Ala). The valine residue is highly conserved and there is a small physicochemical difference between valine and alanine.

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

Last Updated: Nov 10, 2024