NM_000546.6(TP53):c.313G>A (p.Gly105Ser) AND Li-Fraumeni syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 15, 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:: RCV001379190.10

Allele description [Variation Report for NM_000546.6(TP53):c.313G>A (p.Gly105Ser)]

NM_000546.6(TP53):c.313G>A (p.Gly105Ser)

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.313G>A (p.Gly105Ser)

HGVS:

NC_000017.11:g.7676056C>T
NG_017013.2:g.16495G>A
NM_000546.6:c.313G>AMANE SELECT
NM_001126112.3:c.313G>A
NM_001126113.3:c.313G>A
NM_001126114.3:c.313G>A
NM_001126118.2:c.196G>A
NM_001276695.3:c.196G>A
NM_001276696.3:c.196G>A
NM_001276760.3:c.196G>A
NM_001276761.3:c.196G>A
NP_000537.3:p.Gly105Ser
NP_001119584.1:p.Gly105Ser
NP_001119585.1:p.Gly105Ser
NP_001119586.1:p.Gly105Ser
NP_001119590.1:p.Gly66Ser
NP_001263624.1:p.Gly66Ser
NP_001263625.1:p.Gly66Ser
NP_001263689.1:p.Gly66Ser
NP_001263690.1:p.Gly66Ser
LRG_321:g.16495G>A
NC_000017.10:g.7579374C>T
NM_000546.4:c.313G>A
NM_001276760.2:c.196G>A

Protein change:

G105S

Links:

dbSNP: rs1060501195

Molecular consequence:

NM_000546.6:c.313G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.313G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.313G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.313G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.196G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.196G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.196G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.196G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.196G>A - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001576941	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 15, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 30840781, 12826609, 29979965, 30224644, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001576941

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 15, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A quantitative model to predict pathogenicity of missense variants in the TP53 gene.

Fortuno C, Cipponi A, Ballinger ML, Tavtigian SV, Olivier M, Ruparel V, Haupt Y, Haupt S, Study ISK, Tucker K, Spurdle AB, Thomas DM, James PA.

Hum Mutat. 2019 Jun;40(6):788-800. doi: 10.1002/humu.23739. Epub 2019 Mar 18.

PubMed [citation]

PMID:: 30840781

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

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001576941.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 105 of the TP53 protein (p.Gly105Ser). This missense change has been observed in individuals with clinical features of Li-Fraumeni syndrome (Invitae; external communications). This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly105 amino acid residue in TP53. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12826609; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on TP53 function (PMID: 12826609, 29979965, 30224644, 30840781). 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. ClinVar contains an entry for this variant (Variation ID: 428884).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 12, 2026

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