NM_000546.6(TP53):c.849_877dup (p.Gly293fs) AND Li-Fraumeni syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 21, 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:: RCV003622914.2

Allele description [Variation Report for NM_000546.6(TP53):c.849_877dup (p.Gly293fs)]

NM_000546.6(TP53):c.849_877dup (p.Gly293fs)

Gene:

TP53:tumor protein p53 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_000546.6(TP53):c.849_877dup (p.Gly293fs)

HGVS:

NC_000017.11:g.7673744_7673772dup
NG_017013.2:g.18780_18808dup
NM_000546.6:c.849_877dupMANE SELECT
NM_001126112.3:c.849_877dup
NM_001126113.3:c.849_877dup
NM_001126114.3:c.849_877dup
NM_001126115.2:c.453_481dup
NM_001126116.2:c.453_481dup
NM_001126117.2:c.453_481dup
NM_001126118.2:c.732_760dup
NM_001276695.3:c.732_760dup
NM_001276696.3:c.732_760dup
NM_001276697.3:c.372_400dup
NM_001276698.3:c.372_400dup
NM_001276699.3:c.372_400dup
NM_001276760.3:c.732_760dup
NM_001276761.3:c.732_760dup
NM_001407262.1:c.849_877dup
NM_001407263.1:c.732_760dup
NM_001407264.1:c.849_877dup
NM_001407265.1:c.732_760dup
NM_001407266.1:c.849_877dup
NM_001407267.1:c.732_760dup
NM_001407268.1:c.849_877dup
NM_001407269.1:c.732_760dup
NM_001407270.1:c.849_877dup
NM_001407271.1:c.732_760dup
NP_000537.3:p.Gly293Alafs
NP_000537.3:p.Gly293fs
NP_001119584.1:p.Gly293Alafs
NP_001119584.1:p.Gly293fs
NP_001119585.1:p.Gly293Alafs
NP_001119585.1:p.Gly293fs
NP_001119586.1:p.Gly293Alafs
NP_001119586.1:p.Gly293fs
NP_001119587.1:p.Gly161Alafs
NP_001119587.1:p.Gly161fs
NP_001119588.1:p.Gly161Alafs
NP_001119588.1:p.Gly161fs
NP_001119589.1:p.Gly161Alafs
NP_001119589.1:p.Gly161fs
NP_001119590.1:p.Gly254Alafs
NP_001119590.1:p.Gly254fs
NP_001263624.1:p.Gly254fs
NP_001263625.1:p.Gly254fs
NP_001263626.1:p.Gly134fs
NP_001263627.1:p.Gly134fs
NP_001263628.1:p.Gly134fs
NP_001263689.1:p.Gly254fs
NP_001263690.1:p.Gly254fs
NP_001394191.1:p.Gly293fs
NP_001394192.1:p.Gly254fs
NP_001394193.1:p.Gly293fs
NP_001394194.1:p.Gly254fs
NP_001394195.1:p.Gly293fs
NP_001394196.1:p.Gly254fs
NP_001394197.1:p.Gly293fs
NP_001394198.1:p.Gly254fs
NP_001394199.1:p.Gly293fs
NP_001394200.1:p.Gly254fs
LRG_321t1:c.848_876dup
LRG_321t2:c.848_876dup
LRG_321t3:c.848_876dup
LRG_321t4:c.848_876dup
LRG_321t5:c.452_480dup
LRG_321t6:c.452_480dup
LRG_321t7:c.452_480dup
LRG_321t8:c.731_759dup
LRG_321:g.18780_18808dup
LRG_321:p.Gly293Alafs
LRG_321p1:p.Gly293Alafs
LRG_321p3:p.Gly293Alafs
LRG_321p4:p.Gly293Alafs
LRG_321p5:p.Gly161Alafs
LRG_321p6:p.Gly161Alafs
LRG_321p7:p.Gly161Alafs
LRG_321p8:p.Gly254Alafs
NC_000017.10:g.7577060_7577061insCTTTCTTGCGGAGATTCTCTTCCTCTGTG
NC_000017.10:g.7577062_7577090dup
NM_000546.5:c.848_876dup
NM_001126112.2:c.848_876dup
NM_001126113.2:c.848_876dup
NM_001126114.2:c.848_876dup
NM_001126115.1:c.452_480dup
NM_001126116.1:c.452_480dup
NM_001126117.1:c.452_480dup
NM_001126118.1:c.731_759dup
NR_176326.1:n.878_906dup

Protein change:

G134fs

Molecular consequence:

NM_000546.6:c.849_877dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126112.3:c.849_877dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126113.3:c.849_877dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126114.3:c.849_877dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126115.2:c.453_481dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126116.2:c.453_481dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126117.2:c.453_481dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126118.2:c.732_760dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276695.3:c.732_760dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276696.3:c.732_760dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276697.3:c.372_400dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276698.3:c.372_400dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276699.3:c.372_400dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276760.3:c.732_760dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276761.3:c.732_760dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407262.1:c.849_877dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407263.1:c.732_760dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407264.1:c.849_877dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407265.1:c.732_760dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407266.1:c.849_877dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407267.1:c.732_760dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407268.1:c.849_877dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407269.1:c.732_760dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407270.1:c.849_877dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407271.1:c.732_760dup - frameshift variant - [Sequence Ontology: SO:0001589]
NR_176326.1:n.878_906dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV004434872	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 21, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 9766574, 19714490, 25226867, 25981898, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004434872

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 21, 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

Characterization of p53 mutants identified in human tumors with a missense mutation in the tetramerization domain.

Rollenhagen C, Chène P.

Int J Cancer. 1998 Oct 29;78(3):372-6.

PubMed [citation]

PMID:: 9766574

p53 Tetramerization domain mutations: germline R342X and R342P, and somatic R337G identified in pediatric patients with Li-Fraumeni syndrome and a child with adrenocortical carcinoma.

Fiszer-Maliszewska L, Kazanowska B, Padzik J; Regional Blood Transfusion Center..

Fam Cancer. 2009;8(4):541-6. doi: 10.1007/s10689-009-9284-2.

PubMed [citation]

PMID:: 19714490

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004434872.1

#	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 creates a premature translational stop signal (p.Gly293Alafs*62) in the TP53 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 39 amino acid(s) of the TP53 protein. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the TP53 protein in which other variant(s) (p.Arg342Pro) have been determined to be pathogenic (PMID: 9766574, 19714490, 25226867, 25981898). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with TP53-related conditions. This variant is not present in population databases (gnomAD no frequency).

#	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: Sep 29, 2024

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