NM_003001.5(SDHC):c.379C>G (p.His127Asp) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 10, 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:: RCV003101258.4

Allele description [Variation Report for NM_003001.5(SDHC):c.379C>G (p.His127Asp)]

NM_003001.5(SDHC):c.379C>G (p.His127Asp)

Gene:

SDHC:succinate dehydrogenase complex subunit C [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q23.3

Genomic location:

Preferred name:

NM_003001.5(SDHC):c.379C>G (p.His127Asp)

HGVS:

NC_000001.11:g.161356814C>G
NG_012767.1:g.47439C>G
NM_001035511.3:c.242-5515C>G
NM_001035512.3:c.277C>G
NM_001035513.3:c.220C>G
NM_001278172.3:c.140-5515C>G
NM_001407115.1:c.499C>G
NM_001407116.1:c.322C>G
NM_001407117.1:c.316C>G
NM_001407118.1:c.271C>G
NM_001407119.1:c.268C>G
NM_001407120.1:c.268C>G
NM_001407121.1:c.185-5515C>G
NM_003001.5:c.379C>GMANE SELECT
NP_001030589.1:p.His93Asp
NP_001030590.1:p.His74Asp
NP_001394044.1:p.His167Asp
NP_001394045.1:p.His108Asp
NP_001394046.1:p.His106Asp
NP_001394047.1:p.His91Asp
NP_001394048.1:p.His90Asp
NP_001394049.1:p.His90Asp
NP_002992.1:p.His127Asp
NP_002992.1:p.His127Asp
LRG_317t1:c.379C>G
LRG_317:g.47439C>G
LRG_317p1:p.His127Asp
NC_000001.10:g.161326604C>G
NM_003001.3:c.379C>G
NR_103459.3:n.431C>G

Protein change:

H106D

Links:

dbSNP: rs1485675090

NCBI 1000 Genomes Browser:

rs1485675090

Molecular consequence:

NM_001035511.3:c.242-5515C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001278172.3:c.140-5515C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001407121.1:c.185-5515C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001035512.3:c.277C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001035513.3:c.220C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407115.1:c.499C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407116.1:c.322C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407117.1:c.316C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407118.1:c.271C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407119.1:c.268C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407120.1:c.268C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_003001.5:c.379C>G - missense variant - [Sequence Ontology: SO:0001583]
NR_103459.3:n.431C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Gastrointestinal stromal tumor
Synonyms:: Gastrointestinal Stromal Sarcoma; Gastrointestinal stromal tumor, somatic; Gastrointestinal stroma tumor
Identifiers:: MONDO: MONDO:0011719; MeSH: D046152; MedGen: C0238198; Orphanet: 44890; OMIM: 606764; Human Phenotype Ontology: HP:0100723

Name:: Paragangliomas 3 (PPGL3)
Synonyms:: Glomus tumors, familial, 3; SDHC-Related Hereditary Paraganglioma-Pheochromocytoma Syndrome (Paragangliomas 3); PHEOCHROMOCYTOMA/PARAGANGLIOMA SYNDROME 3
Identifiers:: MONDO: MONDO:0011544; MedGen: C1854336; Orphanet: 29072; OMIM: 605373

Recent activity

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ankyrin repeat/KH domain protein (DUF1442) [Arabidopsis thaliana]
ankyrin repeat/KH domain protein (DUF1442) [Arabidopsis thaliana]
gi|15225459|ref|NP_182061.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002977324	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 10, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 22517557, 23162105, 24758179, 26273102, 30050099, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002977324

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 10, 2023)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A decade (2001-2010) of genetic testing for pheochromocytoma and paraganglioma.

Buffet A, Venisse A, Nau V, Roncellin I, Boccio V, Le Pottier N, Boussion M, Travers C, Simian C, Burnichon N, Abermil N, Favier J, Jeunemaitre X, Gimenez-Roqueplo AP.

Horm Metab Res. 2012 May;44(5):359-66. doi: 10.1055/s-0032-1304594. Epub 2012 Apr 19. Review.

PubMed [citation]

PMID:: 22517557

Imaging work-up for screening of paraganglioma and pheochromocytoma in SDHx mutation carriers: a multicenter prospective study from the PGL.EVA Investigators.

Gimenez-Roqueplo AP, Caumont-Prim A, Houzard C, Hignette C, Hernigou A, Halimi P, Niccoli P, Leboulleux S, Amar L, Borson-Chazot F, Cardot-Bauters C, Delemer B, Chabolle F, Coupier I, Libé R, Peitzsch M, Peyrard S, Tenenbaum F, Plouin PF, Chatellier G, Rohmer V.

J Clin Endocrinol Metab. 2013 Jan;98(1):E162-73. doi: 10.1210/jc.2012-2975. Epub 2012 Nov 15.

PubMed [citation]

PMID:: 23162105

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002977324.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

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. This variant disrupts the p.His127 amino acid residue in SDHC. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22517557, 23162105, 24758179, 26273102, 30050099). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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) performed at Invitae indicates that this missense variant is expected to disrupt SDHC protein function. ClinVar contains an entry for this variant (Variation ID: 1677290). This variant has not been reported in the literature in individuals affected with SDHC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with aspartic acid, which is acidic and polar, at codon 127 of the SDHC protein (p.His127Asp).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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