NM_003002.4(SDHD):c.278A>G (p.Tyr93Cys) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Oct 26, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000231432.8

Allele description [Variation Report for NM_003002.4(SDHD):c.278A>G (p.Tyr93Cys)]

NM_003002.4(SDHD):c.278A>G (p.Tyr93Cys)

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.278A>G (p.Tyr93Cys)
HGVS:
  • NC_000011.10:g.112088975A>G
  • NG_012337.3:g.7129A>G
  • NG_033145.1:g.2824T>C
  • NM_001276503.2:c.169+1002A>G
  • NM_001276504.2:c.161A>G
  • NM_001276506.2:c.278A>G
  • NM_003002.4:c.278A>GMANE SELECT
  • NP_001263433.1:p.Tyr54Cys
  • NP_001263435.1:p.Tyr93Cys
  • NP_002993.1:p.Tyr93Cys
  • LRG_9t1:c.278A>G
  • LRG_9:g.7129A>G
  • LRG_9p1:p.Tyr93Cys
  • NC_000011.9:g.111959699A>G
  • NM_003002.2:c.278A>G
  • NM_003002.3:c.278A>G
  • NR_077060.2:n.313A>G
  • p.Y93C
Protein change:
Y54C
Links:
dbSNP: rs142135772
NCBI 1000 Genomes Browser:
rs142135772
Molecular consequence:
  • NM_001276503.2:c.169+1002A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001276504.2:c.161A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276506.2:c.278A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003002.4:c.278A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_077060.2:n.313A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Carney-Stratakis syndrome
Synonyms:
Paraganglioma and gastric stromal sarcoma; Paraganglioma and gastrointestinal stromal tumor; Paraganglioma and GIST; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0011740; MedGen: C1847319; Orphanet: 97286; OMIM: 606864
Name:
Pheochromocytoma
Synonyms:
Chromaffinoma; Chromaffin paraganglioma; Chromaffin tumor; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008233; MedGen: C0031511; Orphanet: 29072; OMIM: 171300; Human Phenotype Ontology: HP:0002666
Name:
Paragangliomas 1 (PGL1)
Synonyms:
PARAGANGLIOMAS, FAMILIAL NONCHROMAFFIN, 1; PGL 1; Paragangliomas familial 1; See all synonyms [MedGen]
Identifiers:
MedGen: C1868633; Orphanet: 29072; OMIM: 168000
Name:
Cowden syndrome 3 (CWS3)
Identifiers:
MONDO: MONDO:0014045; MedGen: CN166604; Orphanet: 201

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000287822Invitaecriteria provided, single submitter
Uncertain significance
(Oct 26, 2020)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Germline PTEN, SDHB-D, and KLLN alterations in endometrial cancer patients with Cowden and Cowden-like syndromes: an international, multicenter, prospective study.

Mahdi H, Mester JL, Nizialek EA, Ngeow J, Michener C, Eng C.

Cancer. 2015 Mar 1;121(5):688-96. doi: 10.1002/cncr.29106. Epub 2014 Nov 5.

PubMed [citation]
PMID:
25376524
PMCID:
PMC4339629

No evidence for involvement of SDHD in neuroblastoma pathogenesis.

De Preter K, Vandesompele J, Hoebeeck J, Vandenbroecke C, Smet J, Nuyts A, Laureys G, Combaret V, Van Roy N, Roels F, Van Coster R, Praet M, De Paepe A, Speleman F.

BMC Cancer. 2004 Aug 24;4:55.

PubMed [citation]
PMID:
15331017
PMCID:
PMC517501
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000287822.8

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces tyrosine with cysteine at codon 93 of the SDHD protein (p.Tyr93Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs142135772, ExAC 0.1%). This variant has been reported in individuals affected with Cowden syndrome (PMID: 25376524). ClinVar contains an entry for this variant (Variation ID: 135197). An experimental study has shown that this missense change does not affect SDHD protein expression, enzymatic activity, or mitochondrial morphology in a cultured neuroblastoma cell line (PMID: 15331017). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Dec 2, 2021

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