U.S. flag

An official website of the United States government

NM_000546.6(TP53):c.607G>A (p.Val203Met) AND Li-Fraumeni syndrome 1

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jun 2, 2021
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
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:
RCV001527100.3

Allele description [Variation Report for NM_000546.6(TP53):c.607G>A (p.Val203Met)]

NM_000546.6(TP53):c.607G>A (p.Val203Met)

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.607G>A (p.Val203Met)
Other names:
p.V203M:GTG>ATG
HGVS:
  • NC_000017.11:g.7674924C>T
  • NG_017013.2:g.17627G>A
  • NM_000546.6:c.607G>AMANE SELECT
  • NM_001126112.3:c.607G>A
  • NM_001126113.3:c.607G>A
  • NM_001126114.3:c.607G>A
  • NM_001126115.2:c.211G>A
  • NM_001126116.2:c.211G>A
  • NM_001126117.2:c.211G>A
  • NM_001126118.2:c.490G>A
  • NM_001276695.3:c.490G>A
  • NM_001276696.3:c.490G>A
  • NM_001276697.3:c.130G>A
  • NM_001276698.3:c.130G>A
  • NM_001276699.3:c.130G>A
  • NM_001276760.3:c.490G>A
  • NM_001276761.3:c.490G>A
  • NP_000537.3:p.Val203Met
  • NP_000537.3:p.Val203Met
  • NP_001119584.1:p.Val203Met
  • NP_001119585.1:p.Val203Met
  • NP_001119586.1:p.Val203Met
  • NP_001119587.1:p.Val71Met
  • NP_001119588.1:p.Val71Met
  • NP_001119589.1:p.Val71Met
  • NP_001119590.1:p.Val164Met
  • NP_001263624.1:p.Val164Met
  • NP_001263625.1:p.Val164Met
  • NP_001263626.1:p.Val44Met
  • NP_001263627.1:p.Val44Met
  • NP_001263628.1:p.Val44Met
  • NP_001263689.1:p.Val164Met
  • NP_001263690.1:p.Val164Met
  • LRG_321t1:c.607G>A
  • LRG_321t2:c.607G>A
  • LRG_321:g.17627G>A
  • LRG_321p1:p.Val203Met
  • NC_000017.10:g.7578242C>T
  • NM_000546.4:c.607G>A
  • NM_000546.5:c.607G>A
  • NM_001126112.2(TP53):c.607G>A
  • P04637:p.Val203Met
Protein change:
V164M
Links:
UniProtKB: P04637#VAR_045039; dbSNP: rs730882003
NCBI 1000 Genomes Browser:
rs730882003
Molecular consequence:
  • NM_000546.6:c.607G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.607G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.3:c.607G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.3:c.607G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126115.2:c.211G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126116.2:c.211G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126117.2:c.211G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.2:c.490G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.3:c.490G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.3:c.490G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276697.3:c.130G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276698.3:c.130G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276699.3:c.130G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.3:c.490G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.3:c.490G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Li-Fraumeni syndrome 1 (LFS)
Identifiers:
Gene: 553989; MedGen: C1835398; Orphanet: 524; OMIM: 151623

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001737945ClinGen TP53 Variant Curation Expert Panel, ClinGen
reviewed by expert panel

(ClinGen TP53 ACMG Specifications v1)		Uncertain significance
(Jun 2, 2021) 		germlinecuration

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Details of each submission

From ClinGen TP53 Variant Curation Expert Panel, ClinGen, SCV001737945.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

This variant is absent from the gnomAD non-cancer v2.1.1 dataset (PM2_supporting). Transactivation assays show partial function according to Kato, et al (PMID: 12826609) with evidence of a dominant negative effect, but not loss of function according to Giacomelli, et al. (PMID: 30224644) and Kotler et al. (PMID: 29979965) (BS3_supporting). The VCEP considers the variant scores borderline/conflicting and therefore overrode application of the BS3_Supporting code. This variant has a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 (BP4). This variant has been identified in one pediatric patient with adrenocortical tumor (PMID: 33178583) and in one patient meeting Chompret criteria (internal laboratory contributor) (PS4_supporting). In summary, TP53 c.607G>A; p.Val203Met meets criteria to be classified as uncertain for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: PM2_supporting; BP4, PS4_supporting.

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

Last Updated: Sep 29, 2024