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NM_000548.5(TSC2):c.4584G>T (p.Glu1528Asp) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jul 20, 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:
RCV001022737.5

Allele description [Variation Report for NM_000548.5(TSC2):c.4584G>T (p.Glu1528Asp)]

NM_000548.5(TSC2):c.4584G>T (p.Glu1528Asp)

Gene:
TSC2:TSC complex subunit 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16p13.3
Genomic location:
Preferred name:
NM_000548.5(TSC2):c.4584G>T (p.Glu1528Asp)
HGVS:
  • NC_000016.10:g.2085244G>T
  • NG_005895.1:g.40939G>T
  • NM_000548.5:c.4584G>TMANE SELECT
  • NM_001077183.3:c.4383G>T
  • NM_001114382.3:c.4515G>T
  • NM_001318827.2:c.4275G>T
  • NM_001318829.2:c.4239G>T
  • NM_001318831.2:c.3852G>T
  • NM_001318832.2:c.4416G>T
  • NM_001363528.2:c.4386G>T
  • NM_001370404.1:c.4452G>T
  • NM_001370405.1:c.4455G>T
  • NM_021055.3:c.4455G>T
  • NP_000539.2:p.Glu1528Asp
  • NP_001070651.1:p.Glu1461Asp
  • NP_001107854.1:p.Glu1505Asp
  • NP_001305756.1:p.Glu1425Asp
  • NP_001305758.1:p.Glu1413Asp
  • NP_001305760.1:p.Glu1284Asp
  • NP_001305761.1:p.Glu1472Asp
  • NP_001350457.1:p.Glu1462Asp
  • NP_001357333.1:p.Glu1484Asp
  • NP_001357334.1:p.Glu1485Asp
  • NP_066399.2:p.Glu1485Asp
  • LRG_487t1:c.4584G>T
  • LRG_487:g.40939G>T
  • NC_000016.9:g.2135245G>T
  • NM_000548.3:c.4584G>T
Protein change:
E1284D
Links:
dbSNP: rs199848388
NCBI 1000 Genomes Browser:
rs199848388
Molecular consequence:
  • NM_000548.5:c.4584G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001077183.3:c.4383G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001114382.3:c.4515G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001318827.2:c.4275G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001318829.2:c.4239G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001318831.2:c.3852G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001318832.2:c.4416G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001363528.2:c.4386G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001370404.1:c.4452G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001370405.1:c.4455G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_021055.3:c.4455G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001184507Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Jul 20, 2023) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes.

Johnston JJ, Rubinstein WS, Facio FM, Ng D, Singh LN, Teer JK, Mullikin JC, Biesecker LG.

Am J Hum Genet. 2012 Jul 13;91(1):97-108. doi: 10.1016/j.ajhg.2012.05.021. Epub 2012 Jun 14.

PubMed [citation]
PMID:
22703879
PMCID:
PMC3397257

Details of each submission

From Ambry Genetics, SCV001184507.6

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

Description

The p.E1528D variant (also known as c.4584G>T), located in coding exon 35 of the TSC2 gene, results from a G to T substitution at nucleotide position 4584. The glutamic acid at codon 1528 is replaced by aspartic acid, an amino acid with highly similar properties. This variant was detected as a secondary finding in 1 out of 572 ClinSeq participants, unselected for personal or family history of cancer, who underwent exome sequencing; however, the clinical information for this particular individual was not provided (Johnston JJ et al. Am. J. Hum. Genet., 2012 Jul;91:97-108). This amino acid position is well conserved in available vertebrate species. In addition, as a missense variant, this alteration is predicted to be tolerated by in silico analysis. In silico splice site analysis predicts that this alteration will result in the creation or strengthening of a novel splice acceptor site; however, direct evidence is insufficient at this time (Ambry internal data).. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

Last Updated: May 1, 2024