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NM_003002.4(SDHD):c.305A>G (p.His102Arg) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 15, 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:
RCV002538159.9

Allele description [Variation Report for NM_003002.4(SDHD):c.305A>G (p.His102Arg)]

NM_003002.4(SDHD):c.305A>G (p.His102Arg)

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.305A>G (p.His102Arg)
HGVS:
  • NC_000011.10:g.112089002A>G
  • NG_012337.3:g.7156A>G
  • NG_033145.1:g.2797T>C
  • NM_001276503.2:c.169+1029A>G
  • NM_001276504.2:c.188A>G
  • NM_001276506.2:c.305A>G
  • NM_003002.4:c.305A>GMANE SELECT
  • NP_001263433.1:p.His63Arg
  • NP_001263435.1:p.His102Arg
  • NP_002993.1:p.His102Arg
  • LRG_9t1:c.305A>G
  • LRG_9:g.7156A>G
  • LRG_9p1:p.His102Arg
  • NC_000011.9:g.111959726A>G
  • NM_003002.2:c.305A>G
  • NM_003002.3:c.305A>G
  • NR_077060.2:n.340A>G
Protein change:
H102R
Links:
dbSNP: rs104894302
NCBI 1000 Genomes Browser:
rs104894302
Molecular consequence:
  • NM_001276503.2:c.169+1029A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001276504.2:c.188A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276506.2:c.305A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003002.4:c.305A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_077060.2:n.340A>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 with sensorineural hearing loss (PGL1)
Identifiers:
MedGen: C1868633
Name:
Cowden syndrome 3 (CWS3)
Identifiers:
MONDO: MONDO:0014045; MedGen: CN166604; Orphanet: 201

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000953725Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Oct 15, 2023) 		germlineclinical testing

PubMed (8)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Novel SDHD gene mutation (H102R) in a patient with metastatic cervical paraganglioma effectively treated by peptide receptor radionuclide therapy.

Poeppel TD, Yuece A, Boy C, Metz KA, Kaminsky E, Neumann HP, Rosenbaum SJ, Mann K, Moeller LC.

J Clin Oncol. 2011 Nov 20;29(33):e812-5. doi: 10.1200/JCO.2011.36.2269. Epub 2011 Oct 24. No abstract available.

PubMed [citation]
PMID:
22025150

The spectrum of SDHD mutations in Russian patients with head and neck paraganglioma.

Shulskaya MV, Shadrina MI, Bakilina NA, Zolotova SV, Slominsky PA.

Int J Neurosci. 2018 Dec;128(12):1174-1179. doi: 10.1080/00207454.2018.1503181. Epub 2018 Oct 30.

PubMed [citation]
PMID:
30375904
See all PubMed Citations (8)

Details of each submission

From Invitae, SCV000953725.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 102 of the SDHD protein (p.His102Arg). This variant is present in population databases (rs104894302, gnomAD 0.0009%). This missense change has been observed in individuals with clinical features of hereditary paraganglioma-pheochromocytoma syndrome (PMID: 22025150, 30375904, 36614070). ClinVar contains an entry for this variant (Variation ID: 656860). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SDHD protein function. This variant disrupts the p.His102 amino acid residue in SDHD. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10657297, 12811540, 19454582, 22241717). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: May 1, 2024