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NM_000546.6(TP53):c.581T>G (p.Leu194Arg) AND Hereditary breast ovarian cancer syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
May 14, 2024
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:
RCV004764786.1

Allele description [Variation Report for NM_000546.6(TP53):c.581T>G (p.Leu194Arg)]

NM_000546.6(TP53):c.581T>G (p.Leu194Arg)

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.581T>G (p.Leu194Arg)
HGVS:
  • NC_000017.11:g.7674950A>C
  • NG_017013.2:g.17601T>G
  • NM_000546.6:c.581T>GMANE SELECT
  • NM_001126112.3:c.581T>G
  • NM_001126113.3:c.581T>G
  • NM_001126114.3:c.581T>G
  • NM_001126115.2:c.185T>G
  • NM_001126116.2:c.185T>G
  • NM_001126117.2:c.185T>G
  • NM_001126118.2:c.464T>G
  • NM_001276695.3:c.464T>G
  • NM_001276696.3:c.464T>G
  • NM_001276697.3:c.104T>G
  • NM_001276698.3:c.104T>G
  • NM_001276699.3:c.104T>G
  • NM_001276760.3:c.464T>G
  • NM_001276761.3:c.464T>G
  • NP_000537.3:p.Leu194Arg
  • NP_000537.3:p.Leu194Arg
  • NP_001119584.1:p.Leu194Arg
  • NP_001119585.1:p.Leu194Arg
  • NP_001119586.1:p.Leu194Arg
  • NP_001119587.1:p.Leu62Arg
  • NP_001119588.1:p.Leu62Arg
  • NP_001119589.1:p.Leu62Arg
  • NP_001119590.1:p.Leu155Arg
  • NP_001263624.1:p.Leu155Arg
  • NP_001263625.1:p.Leu155Arg
  • NP_001263626.1:p.Leu35Arg
  • NP_001263627.1:p.Leu35Arg
  • NP_001263628.1:p.Leu35Arg
  • NP_001263689.1:p.Leu155Arg
  • NP_001263690.1:p.Leu155Arg
  • LRG_321t1:c.581T>G
  • LRG_321:g.17601T>G
  • LRG_321p1:p.Leu194Arg
  • NC_000017.10:g.7578268A>C
  • NM_000546.4:c.581T>G
  • NM_000546.5:c.581T>G
Protein change:
L155R
Links:
dbSNP: rs1057519998
NCBI 1000 Genomes Browser:
rs1057519998
Molecular consequence:
  • NM_000546.6:c.581T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.581T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.3:c.581T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.3:c.581T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126115.2:c.185T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126116.2:c.185T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126117.2:c.185T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.2:c.464T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.3:c.464T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.3:c.464T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276697.3:c.104T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276698.3:c.104T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276699.3:c.104T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.3:c.464T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.3:c.464T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary breast ovarian cancer syndrome
Synonyms:
Hereditary breast and ovarian cancer syndrome; Hereditary breast and ovarian cancer; Hereditary breast and ovarian cancer syndrome (HBOC); See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0003582; MeSH: D061325; MedGen: C0677776; Orphanet: 145

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005374679German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne
criteria provided, single submitter

(ClinGen TP53 V1.4.0)		Likely pathogenic
(May 14, 2024) 		germlinecuration

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedcuration

Details of each submission

From German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne, SCV005374679.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

According to the ClinGen ACMG TP53 v1.4.0 criteria we chose these criteria: PS3 (strong pathogenic): Giacomelli 2018: DNE and LOF, Kato 2003: non funct ClinGen-TP3-PS3-str: transactivation assays in yeast (IARC classification based on data from Kato et al, 2003) that demonstrate a low functioning allele (<= 20% activity) AND: Evidence of dominant negative effect (DNE) + evidence of LOF from Giacomelli, et al data , PM1 (medium pathogenic): This rule can be applied to variants in hot spots (codons 175, 245, 248, 249, 273, 282), but not to variants within functional domains. Use transcript NM_000546.4. Also use rule for variants with ≥10 somatic observations cancerhotspots.org (v2) L194: 49x in cancerhotspots, PM2 (supporting pathogenic): 1X in gnomAD, PP3 (medium pathogenic): BayesDel (no AF): 0.582962 AlignGVGD: C65

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

Last Updated: May 16, 2025