NM_000546.6(TP53):c.214_215delinsTG (p.Pro72Cys) AND Li-Fraumeni syndrome

Clinical significance:Uncertain significance (Last evaluated: Sep 8, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_000546.6(TP53):c.214_215delinsTG (p.Pro72Cys)]

NM_000546.6(TP53):c.214_215delinsTG (p.Pro72Cys)

TP53:tumor protein p53 [Gene - OMIM - HGNC]
Variant type:
Cytogenetic location:
Genomic location:
Preferred name:
NM_000546.6(TP53):c.214_215delinsTG (p.Pro72Cys)
Other names:
  • NC_000017.11:g.7676154_7676155delinsCA
  • NG_017013.2:g.16396_16397delinsTG
  • NM_000546.5:c.214_215delinsTG
  • NM_000546.6:c.214_215delinsTGMANE SELECT
  • NM_001126112.3:c.214_215delinsTG
  • NM_001126113.3:c.214_215delinsTG
  • NM_001126114.3:c.214_215delinsTG
  • NM_001126118.2:c.97_98delinsTG
  • NM_001276695.3:c.97_98delinsTG
  • NM_001276696.3:c.97_98delinsTG
  • NM_001276760.3:c.97_98delinsTG
  • NM_001276761.3:c.97_98delinsTG
  • NP_000537.3:p.Pro72Cys
  • NP_000537.3:p.Pro72Cys
  • NP_001119584.1:p.Pro72Cys
  • NP_001119585.1:p.Pro72Cys
  • NP_001119586.1:p.Pro72Cys
  • NP_001119590.1:p.Pro33Cys
  • NP_001263624.1:p.Pro33Cys
  • NP_001263625.1:p.Pro33Cys
  • NP_001263689.1:p.Pro33Cys
  • NP_001263690.1:p.Pro33Cys
  • LRG_321t1:c.214_215delinsTG
  • LRG_321t2:c.214_215delinsTG
  • LRG_321:g.16396_16397delinsTG
  • LRG_321p1:p.Pro72Cys
  • NC_000017.10:g.7579472_7579473delinsCA
  • NM_000546.4:c.214_215delCCinsTG
  • NM_000546.5:c.214_215delCCinsTG
  • NM_001126112.2(TP53):c.214_215delinsTG
  • p.P72C
  • p.Pro72Cys
Protein change:
dbSNP: rs730882014
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000546.5:c.214_215delinsTG - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000546.6:c.214_215delinsTG - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.214_215delinsTG - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.3:c.214_215delinsTG - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.3:c.214_215delinsTG - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.2:c.97_98delinsTG - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.3:c.97_98delinsTG - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.3:c.97_98delinsTG - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.3:c.97_98delinsTG - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.3:c.97_98delinsTG - missense variant - [Sequence Ontology: SO:0001583]


Li-Fraumeni syndrome (LFS)
Sarcoma family syndrome of Li and Fraumeni
MONDO: MONDO:0018875; MedGen: C0085390; OMIM: PS151623

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000629788Invitaecriteria provided, single submitter
Uncertain significance
(Sep 8, 2020)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

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



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):240-242.

PubMed [citation]

Details of each submission

From Invitae, SCV000629788.6

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


This sequence change replaces proline with cysteine at codon 72 of the TP53 protein (p.Pro72Cys). The proline residue is moderately conserved and there is a large physicochemical difference between proline and cysteine. This variant is reported as two separate single-nucleotide changes in the ExAC database (c.214C>T and c.215C>G), but the read data shows that the two variants are in cis, recapitulating the variant observed here (c.214_215delCCinsTG), in one individual. This variant has not been reported in the literature in individuals with TP53-related disease. ClinVar contains an entry for this variant (Variation ID: 182953). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class 0). 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.

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

Last Updated: Nov 27, 2021

Support Center