NM_003002.4(SDHD):c.341A>G (p.Tyr114Cys) AND Hereditary cancer-predisposing syndrome

Clinical significance:Pathogenic (Last evaluated: Sep 28, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000221353.2

Allele description [Variation Report for NM_003002.4(SDHD):c.341A>G (p.Tyr114Cys)]

NM_003002.4(SDHD):c.341A>G (p.Tyr114Cys)

Gene:
SDHD:succinate dehydrogenase complex subunit D [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q23.1
Genomic location:
Preferred name:
NM_003002.4(SDHD):c.341A>G (p.Tyr114Cys)
HGVS:
  • NC_000011.10:g.112094831A>G
  • NG_012337.3:g.12985A>G
  • NM_001276503.2:c.196A>G
  • NM_001276504.2:c.224A>G
  • NM_001276506.2:c.*39A>G
  • NM_003002.4:c.341A>GMANE SELECT
  • NP_001263432.1:p.Met66Val
  • NP_001263433.1:p.Tyr75Cys
  • NP_002993.1:p.Tyr114Cys
  • LRG_9t1:c.341A>G
  • LRG_9:g.12985A>G
  • LRG_9p1:p.Tyr114Cys
  • NC_000011.9:g.111965555A>G
  • NM_003002.2:c.341A>G
  • NM_003002.3:c.341A>G
  • NR_077060.2:n.430A>G
  • O14521:p.Tyr114Cys
Protein change:
M66V; TYR114CYS
Links:
UniProtKB: O14521#VAR_017872; OMIM: 602690.0007; dbSNP: rs104894304
NCBI 1000 Genomes Browser:
rs104894304
Molecular consequence:
  • NM_001276506.2:c.*39A>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001276503.2:c.196A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276504.2:c.224A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003002.4:c.341A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_077060.2:n.430A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
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
SCV000275206Ambry Geneticscriteria provided, single submitter
Pathogenic
(Sep 28, 2017)
germlineclinical testing

PubMed (7)
[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

Novel mutations and the emergence of a common mutation in the SDHD gene causing familial paraganglioma.

Milunsky JM, Maher TA, Michels VV, Milunsky A.

Am J Med Genet. 2001 May 15;100(4):311-4.

PubMed [citation]
PMID:
11343322

Carotid body paraganglioma and SDHD mutation in a Greek family.

Liapis CD, Bellos JK, Halapas A, Lembessis P, Koutsilieris M, Kostakis A.

Anticancer Res. 2005 May-Jun;25(3c):2449-52.

PubMed [citation]
PMID:
16080474
See all PubMed Citations (7)

Details of each submission

From Ambry Genetics, SCV000275206.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (7)

Description

The p.Y114C pathogenic mutation (also known as c.341A>G), located in exon 4 of the SDHD gene, results from an A to G substitution at nucleotide position 341. The tyrosine at codon 114 is replaced by cysteine, an amino acid with highly dissimilar properties. This mutation has been identified in multiple individuals affected with paragangliomas (PGL) and/or pheochromocytomas (Neumann H et al. JAMA. 2004 Aug 25;292(8):943-51; Liapis C et al. Anticancer Res. 2005 May-Jun;25(3c):2449-52; Benn D et al. J. Clin. Endocrinol. Metab. 2006 Mar;91(3):827-36; Antonello M et al. Eur. J. Vasc. Endovasc. Surg. 2008 Nov;36(5):517-9; Piccini V et al. Endocr. Relat. Cancer. 2012 Apr 10;19(2):149-55; Zdrojowy-WeÅ‚na A and Bednarek-Tupikowska G. Neuro Endocrinol. Lett. 2014;35(5):355-8; Bennedbæk M et al. Hered. Cancer Clin. Pract. 2016 Jun;14:13). In addition, this mutation showed strong segregation with disease among 38 screened members of a family affected with head and neck PGL (Fish J et al. Head Neck. 2007 Sep;29(9):864-73). Another study indicated that the p.Y114C mutation in the SDHD gene is an Italian founder mutation after finding this alteration in 287 out of 540 individuals from 95 kindred who were diagnosed with head and neck PGL (Schiavi et al. J. Clin. Endocrinol. Metab. 2012 Apr;97(4):637-41). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Dec 2, 2021

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