NM_000546.6(TP53):c.635_642del (p.Thr211_Phe212insTer) AND Li-Fraumeni syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 23, 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:: RCV003511114.1

Allele description [Variation Report for NM_000546.6(TP53):c.635_642del (p.Thr211_Phe212insTer)]

NM_000546.6(TP53):c.635_642del (p.Thr211_Phe212insTer)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_000546.6(TP53):c.635_642del (p.Thr211_Phe212insTer)

HGVS:

NC_000017.11:g.7674890_7674897del
NG_017013.2:g.17655_17662del
NM_000546.6:c.635_642delMANE SELECT
NM_001126112.3:c.635_642del
NM_001126113.3:c.635_642del
NM_001126114.3:c.635_642del
NM_001126115.2:c.239_246del
NM_001126116.2:c.239_246del
NM_001126117.2:c.239_246del
NM_001126118.2:c.518_525del
NM_001276695.3:c.518_525del
NM_001276696.3:c.518_525del
NM_001276697.3:c.158_165del
NM_001276698.3:c.158_165del
NM_001276699.3:c.158_165del
NM_001276760.3:c.518_525del
NM_001276761.3:c.518_525del
NM_001407262.1:c.635_642del
NM_001407263.1:c.518_525del
NM_001407264.1:c.635_642del
NM_001407265.1:c.518_525del
NM_001407266.1:c.635_642del
NM_001407267.1:c.518_525del
NM_001407268.1:c.635_642del
NM_001407269.1:c.518_525del
NM_001407270.1:c.635_642del
NM_001407271.1:c.518_525del
NP_000537.3:p.Phe212Terfs
NP_000537.3:p.Thr211_Phe212insTer
NP_001119584.1:p.Phe212Terfs
NP_001119584.1:p.Thr211_Phe212insTer
NP_001119585.1:p.Phe212Terfs
NP_001119585.1:p.Thr211_Phe212insTer
NP_001119586.1:p.Phe212Terfs
NP_001119586.1:p.Thr211_Phe212insTer
NP_001119587.1:p.Phe80Terfs
NP_001119587.1:p.Thr79_Phe80insTer
NP_001119588.1:p.Phe80Terfs
NP_001119588.1:p.Thr79_Phe80insTer
NP_001119589.1:p.Phe80Terfs
NP_001119589.1:p.Thr79_Phe80insTer
NP_001119590.1:p.Phe173Terfs
NP_001119590.1:p.Thr172_Phe173insTer
NP_001263624.1:p.Thr172_Phe173insTer
NP_001263625.1:p.Thr172_Phe173insTer
NP_001263626.1:p.Thr52_Phe53insTer
NP_001263627.1:p.Thr52_Phe53insTer
NP_001263628.1:p.Thr52_Phe53insTer
NP_001263689.1:p.Thr172_Phe173insTer
NP_001263690.1:p.Thr172_Phe173insTer
NP_001394191.1:p.Thr211_Phe212insTer
NP_001394192.1:p.Thr172_Phe173insTer
NP_001394193.1:p.Thr211_Phe212insTer
NP_001394194.1:p.Thr172_Phe173insTer
NP_001394195.1:p.Thr211_Phe212insTer
NP_001394196.1:p.Thr172_Phe173insTer
NP_001394197.1:p.Thr211_Phe212insTer
NP_001394198.1:p.Thr172_Phe173insTer
NP_001394199.1:p.Thr211_Phe212insTer
NP_001394200.1:p.Thr172_Phe173insTer
LRG_321t1:c.634_641del
LRG_321t2:c.634_641del
LRG_321t3:c.634_641del
LRG_321t4:c.634_641del
LRG_321t5:c.238_245del
LRG_321t6:c.238_245del
LRG_321t7:c.238_245del
LRG_321t8:c.517_524del
LRG_321:g.17655_17662del
LRG_321:p.Phe212Terfs
LRG_321p1:p.Phe212Terfs
LRG_321p3:p.Phe212Terfs
LRG_321p4:p.Phe212Terfs
LRG_321p5:p.Phe80Terfs
LRG_321p6:p.Phe80Terfs
LRG_321p7:p.Phe80Terfs
LRG_321p8:p.Phe173Terfs
NC_000017.10:g.7578207_7578214del
NC_000017.10:g.7578208_7578215del
NM_000546.5:c.634_641delTTTCGACA
NM_001126112.2:c.634_641delTTTCGACA
NM_001126113.2:c.634_641delTTTCGACA
NM_001126114.2:c.634_641delTTTCGACA
NM_001126115.1:c.238_245delTTTCGACA
NM_001126116.1:c.238_245delTTTCGACA
NM_001126117.1:c.238_245delTTTCGACA
NM_001126118.1:c.517_524delTTTCGACA

Molecular consequence:

NM_000546.6:c.635_642del - nonsense - [Sequence Ontology: SO:0001587]
NM_001126112.3:c.635_642del - nonsense - [Sequence Ontology: SO:0001587]
NM_001126113.3:c.635_642del - nonsense - [Sequence Ontology: SO:0001587]
NM_001126114.3:c.635_642del - nonsense - [Sequence Ontology: SO:0001587]
NM_001126115.2:c.239_246del - nonsense - [Sequence Ontology: SO:0001587]
NM_001126116.2:c.239_246del - nonsense - [Sequence Ontology: SO:0001587]
NM_001126117.2:c.239_246del - nonsense - [Sequence Ontology: SO:0001587]
NM_001126118.2:c.518_525del - nonsense - [Sequence Ontology: SO:0001587]
NM_001276695.3:c.518_525del - nonsense - [Sequence Ontology: SO:0001587]
NM_001276696.3:c.518_525del - nonsense - [Sequence Ontology: SO:0001587]
NM_001276697.3:c.158_165del - nonsense - [Sequence Ontology: SO:0001587]
NM_001276698.3:c.158_165del - nonsense - [Sequence Ontology: SO:0001587]
NM_001276699.3:c.158_165del - nonsense - [Sequence Ontology: SO:0001587]
NM_001276760.3:c.518_525del - nonsense - [Sequence Ontology: SO:0001587]
NM_001276761.3:c.518_525del - nonsense - [Sequence Ontology: SO:0001587]
NM_001407262.1:c.635_642del - nonsense - [Sequence Ontology: SO:0001587]
NM_001407263.1:c.518_525del - nonsense - [Sequence Ontology: SO:0001587]
NM_001407264.1:c.635_642del - nonsense - [Sequence Ontology: SO:0001587]
NM_001407265.1:c.518_525del - nonsense - [Sequence Ontology: SO:0001587]
NM_001407266.1:c.635_642del - nonsense - [Sequence Ontology: SO:0001587]
NM_001407267.1:c.518_525del - nonsense - [Sequence Ontology: SO:0001587]
NM_001407268.1:c.635_642del - nonsense - [Sequence Ontology: SO:0001587]
NM_001407269.1:c.518_525del - nonsense - [Sequence Ontology: SO:0001587]
NM_001407270.1:c.635_642del - nonsense - [Sequence Ontology: SO:0001587]
NM_001407271.1:c.518_525del - nonsense - [Sequence Ontology: SO:0001587]

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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RecName: Full=Cytochrome b-c1 complex subunit 7; AltName: Full=Complex III subun...
RecName: Full=Cytochrome b-c1 complex subunit 7; AltName: Full=Complex III subunit 7; AltName: Full=Complex III subunit VII; AltName: Full=QP-C; AltName: Full=Ubiquinol-cytochrome c reductase complex 14 kDa protein
gi|136717|sp|P14927.2|QCR7_HUMAN

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004279078	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 23, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20522432, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004279078

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 23, 2023)

germline

clinical testing

PubMed (2)
[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

TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes.

Ruijs MW, Verhoef S, Rookus MA, Pruntel R, van der Hout AH, Hogervorst FB, Kluijt I, Sijmons RH, Aalfs CM, Wagner A, Ausems MG, Hoogerbrugge N, van Asperen CJ, Gomez Garcia EB, Meijers-Heijboer H, Ten Kate LP, Menko FH, van 't Veer LJ.

J Med Genet. 2010 Jun;47(6):421-8. doi: 10.1136/jmg.2009.073429.

PubMed [citation]

PMID:: 20522432

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV004279078.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Phe212*) in the TP53 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TP53-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#	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: Feb 20, 2024

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