NM_003001.5(SDHC):c.224G>A (p.Gly75Asp) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 1, 2020
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:: RCV000564191.6

Allele description [Variation Report for NM_003001.5(SDHC):c.224G>A (p.Gly75Asp)]

NM_003001.5(SDHC):c.224G>A (p.Gly75Asp)

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.224G>A (p.Gly75Asp)

HGVS:

NC_000001.11:g.161340638G>A
NG_012767.1:g.31263G>A
NM_001035511.3:c.224G>A
NM_001035512.3:c.122G>A
NM_001035513.3:c.65G>A
NM_001278172.3:c.122G>A
NM_001407115.1:c.344G>A
NM_001407116.1:c.167G>A
NM_001407117.1:c.167G>A
NM_001407118.1:c.122G>A
NM_001407119.1:c.113G>A
NM_001407120.1:c.113G>A
NM_001407121.1:c.167G>A
NM_003001.5:c.224G>AMANE SELECT
NP_001030588.1:p.Gly75Asp
NP_001030588.1:p.Gly75Asp
NP_001030589.1:p.Gly41Asp
NP_001030589.1:p.Gly41Asp
NP_001030590.1:p.Gly22Asp
NP_001030590.1:p.Gly22Asp
NP_001265101.1:p.Gly41Asp
NP_001265101.1:p.Gly41Asp
NP_001394044.1:p.Gly115Asp
NP_001394045.1:p.Gly56Asp
NP_001394046.1:p.Gly56Asp
NP_001394047.1:p.Gly41Asp
NP_001394048.1:p.Gly38Asp
NP_001394049.1:p.Gly38Asp
NP_001394050.1:p.Gly56Asp
NP_002992.1:p.Gly75Asp
NP_002992.1:p.Gly75Asp
LRG_317t1:c.224G>A
LRG_317:g.31263G>A
LRG_317p1:p.Gly75Asp
NC_000001.10:g.161310428G>A
NM_001035511.2:c.224G>A
NM_001035512.2:c.122G>A
NM_001035513.2:c.65G>A
NM_001278172.2:c.122G>A
NM_003001.3:c.224G>A
NR_103459.2:n.276G>A
NR_103459.3:n.276G>A

Protein change:

G115D

Links:

dbSNP: rs786205147

NCBI 1000 Genomes Browser:

rs786205147

Molecular consequence:

NM_001035511.3:c.224G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001035512.3:c.122G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001035513.3:c.65G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001278172.3:c.122G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407115.1:c.344G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407116.1:c.167G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407117.1:c.167G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407118.1:c.122G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407119.1:c.113G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407120.1:c.113G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407121.1:c.167G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003001.5:c.224G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000675104	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Pathogenic (Jun 1, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19351833, 21822798, 26173966 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000675104

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Pathogenic
(Jun 1, 2020)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	1	not provided	clinical 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

Thiabendazole inhibits ubiquinone reduction activity of mitochondrial respiratory complex II via a water molecule mediated binding feature.

Zhou Q, Zhai Y, Lou J, Liu M, Pang X, Sun F.

Protein Cell. 2011 Jul;2(7):531-42. doi: 10.1007/s13238-011-1079-1. Epub 2011 Aug 6.

PubMed [citation]

PMID:: 21822798
PMCID:: PMC4875242

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000675104.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (3)

Description

The p.G75D pathogenic mutation (also known as c.224G>A), located in coding exon 4 of the SDHC gene, results from a G to A substitution at nucleotide position 224. The glycine at codon 75 is replaced by aspartic acid, an amino acid with similar properties. In a study of 598 unrelated probands diagnosed with head and neck paraganglioma, this pathogenic variant was detected in 2 individuals (Neumann HP et al. Cancer Res. 2009 Apr;69:3650-6). This pathogenic variant has also been detected in an individual with Carney triad (Boikos SA et al. Eur. J. Hum. Genet. 2016 Apr;24:569-73). Based on internal structural analysis, this variant is anticipated to result in a decrease in structural stability (Ambry internal data; Zhou Q et al. Protein Cell. 2011 Jul;2:531-42). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Apr 15, 2024

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