NM_000546.5(TP53):c.717C>G (p.Asn239Lys) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Sep 7, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000431317.1

Allele description

NM_000546.5(TP53):c.717C>G (p.Asn239Lys)

Gene:
TP53:tumor protein p53 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17p13.1
Genomic location:
Preferred name:
NM_000546.5(TP53):c.717C>G (p.Asn239Lys)
HGVS:
  • NC_000017.11:g.7674246G>C
  • NG_017013.2:g.18305C>G
  • NM_000546.5:c.717C>G
  • NM_001126112.2:c.717C>G
  • NM_001126113.2:c.717C>G
  • NM_001126114.2:c.717C>G
  • NM_001126115.1:c.321C>G
  • NM_001126116.1:c.321C>G
  • NM_001126117.1:c.321C>G
  • NM_001126118.1:c.600C>G
  • NP_000537.3:p.Asn239Lys
  • NP_001119584.1:p.Asn239Lys
  • NP_001119585.1:p.Asn239Lys
  • NP_001119586.1:p.Asn239Lys
  • NP_001119587.1:p.Asn107Lys
  • NP_001119588.1:p.Asn107Lys
  • NP_001119589.1:p.Asn107Lys
  • NP_001119590.1:p.Asn200Lys
  • LRG_321t1:c.717C>G
  • LRG_321t2:c.717C>G
  • LRG_321t3:c.717C>G
  • LRG_321t4:c.717C>G
  • LRG_321t5:c.321C>G
  • LRG_321t6:c.321C>G
  • LRG_321t7:c.321C>G
  • LRG_321t8:c.600C>G
  • LRG_321:g.18305C>G
  • LRG_321p1:p.Asn239Lys
  • LRG_321p3:p.Asn239Lys
  • LRG_321p4:p.Asn239Lys
  • LRG_321p5:p.Asn107Lys
  • LRG_321p6:p.Asn107Lys
  • LRG_321p7:p.Asn107Lys
  • LRG_321p8:p.Asn200Lys
  • NC_000017.10:g.7577564G>C
  • NM_000546.4:c.717C>G
Protein change:
N107K
Links:
dbSNP: rs1057522275
NCBI 1000 Genomes Browser:
rs1057522275
Molecular consequence:
  • NM_000546.5:c.717C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000526938GeneDxcriteria provided, single submitter
Uncertain significance
(Sep 7, 2016)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000526938.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The N239K variant in the TP53 gene has previously been reported as a somatic variant in at least one oral squamous cell carcinoma, but has not been reported in the germline (Yamazaki et al., 2003). In vitro functional studies were inconsistent with regards to transactivation activity; Epstein et al. (1998) reports no residual transactivation activity while Kato et al. (2003) shows residual activity. The N239K variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The N239K variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species, and is located within the DNA binding domain (Bode et al., 2004). Missense variants in nearby residues (Y234H, Y234C, N235D, N235S, Y236D, Y236C, M237I, C238S, C238G, C238Y, S241T, S241F, S241Y, C242R, C242Y, G244S, G244D, G244V) have been reported in the Human Gene Mutation Database in association with TP53-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. Based on the currently available information, it is unclear whether N239K is a pathogenic variant or a rare benign variant. We consider it to be a variant of uncertain significance.

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

Last Updated: Jul 1, 2017