NM_003000.2(SDHB):c.238A>G (p.Lys80Glu) AND Hereditary cancer-predisposing syndrome

Clinical significance:Likely pathogenic (Last evaluated: Aug 7, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000492648.1

Allele description [Variation Report for NM_003000.2(SDHB):c.238A>G (p.Lys80Glu)]

NM_003000.2(SDHB):c.238A>G (p.Lys80Glu)

Gene:
SDHB:succinate dehydrogenase complex iron sulfur subunit B [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p36.13
Genomic location:
Preferred name:
NM_003000.2(SDHB):c.238A>G (p.Lys80Glu)
HGVS:
  • NC_000001.11:g.17033108T>C
  • NG_012340.1:g.26063A>G
  • NM_003000.2:c.238A>G
  • NP_002991.2:p.Lys80Glu
  • LRG_316t1:c.238A>G
  • LRG_316:g.26063A>G
  • LRG_316p1:p.Lys80Glu
  • NC_000001.10:g.17359603T>C
Protein change:
K80E
Links:
dbSNP: rs1131691051
NCBI 1000 Genomes Browser:
rs1131691051
Molecular consequence:
  • NM_003000.2:c.238A>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000581196Ambry Geneticscriteria provided, single submitter
Likely pathogenic
(Aug 7, 2018)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Clinical predictors for germline mutations in head and neck paraganglioma patients: cost reduction strategy in genetic diagnostic process as fall-out.

Neumann HP, Erlic Z, Boedeker CC, Rybicki LA, Robledo M, Hermsen M, Schiavi F, Falcioni M, Kwok P, Bauters C, Lampe K, Fischer M, Edelman E, Benn DE, Robinson BG, Wiegand S, Rasp G, Stuck BA, Hoffmann MM, Sullivan M, Sevilla MA, Weiss MM, et al.

Cancer Res. 2009 Apr 15;69(8):3650-6. doi: 10.1158/0008-5472.CAN-08-4057. Epub 2009 Apr 7.

PubMed [citation]
PMID:
19351833

Yeast model for evaluating the pathogenic significance of SDHB, SDHC and SDHD mutations in PHEO-PGL syndrome.

Panizza E, Ercolino T, Mori L, Rapizzi E, Castellano M, Opocher G, Ferrero I, Neumann HP, Mannelli M, Goffrini P.

Hum Mol Genet. 2013 Feb 15;22(4):804-15. doi: 10.1093/hmg/dds487. Epub 2012 Nov 21.

PubMed [citation]
PMID:
23175444

Details of each submission

From Ambry Genetics, SCV000581196.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (2)

Description

The p.K80E variant (also known as c.238A>G) is located in coding exon 3 of the SDHB gene. This alteration results from a A to G substitution at nucleotide position 238. The lysine at codon 80 is replaced by glutamate, an amino acid with similar properties. This alteration has previously been reported in an individual with a head and neck paraganglioma (Neumann HP et al. Cancer Res. 2009 Apr 15;69(8):3650-6). According to results from a functional study in yeast, this alteration showed no increased sensitivity to oxidative stress and no increase of mitochondrial DNA mutability; however residual SDH enzyme activity was reduced to 50% (Panizza E et al. Hum Mol Genet. 2012 Nov 21). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Oct 8, 2021

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