NM_003001.5(SDHC):c.200T>C (p.Met67Thr) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 27, 2022
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:: RCV000699006.10

Allele description [Variation Report for NM_003001.5(SDHC):c.200T>C (p.Met67Thr)]

NM_003001.5(SDHC):c.200T>C (p.Met67Thr)

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.200T>C (p.Met67Thr)

HGVS:

NC_000001.11:g.161340614T>C
NG_012767.1:g.31239T>C
NM_001035511.3:c.200T>C
NM_001035512.3:c.98T>C
NM_001035513.3:c.41T>C
NM_001278172.3:c.98T>C
NM_001407115.1:c.320T>C
NM_001407116.1:c.143T>C
NM_001407117.1:c.143T>C
NM_001407118.1:c.98T>C
NM_001407119.1:c.89T>C
NM_001407120.1:c.89T>C
NM_001407121.1:c.143T>C
NM_003001.5:c.200T>CMANE SELECT
NP_001030588.1:p.Met67Thr
NP_001030588.1:p.Met67Thr
NP_001030589.1:p.Met33Thr
NP_001030589.1:p.Met33Thr
NP_001030590.1:p.Met14Thr
NP_001030590.1:p.Met14Thr
NP_001265101.1:p.Met33Thr
NP_001265101.1:p.Met33Thr
NP_001394044.1:p.Met107Thr
NP_001394045.1:p.Met48Thr
NP_001394046.1:p.Met48Thr
NP_001394047.1:p.Met33Thr
NP_001394048.1:p.Met30Thr
NP_001394049.1:p.Met30Thr
NP_001394050.1:p.Met48Thr
NP_002992.1:p.Met67Thr
NP_002992.1:p.Met67Thr
LRG_317t1:c.200T>C
LRG_317:g.31239T>C
LRG_317p1:p.Met67Thr
NC_000001.10:g.161310404T>C
NM_001035511.2:c.200T>C
NM_001035512.2:c.98T>C
NM_001035513.2:c.41T>C
NM_001278172.2:c.98T>C
NM_003001.3:c.200T>C
NR_103459.2:n.252T>C
NR_103459.3:n.252T>C

Protein change:

M107T

Links:

dbSNP: rs1287584713

NCBI 1000 Genomes Browser:

rs1287584713

Molecular consequence:

NM_001035511.3:c.200T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001035512.3:c.98T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001035513.3:c.41T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001278172.3:c.98T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407115.1:c.320T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407116.1:c.143T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407117.1:c.143T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407118.1:c.98T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407119.1:c.89T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407120.1:c.89T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407121.1:c.143T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_003001.5:c.200T>C - missense variant - [Sequence Ontology: SO:0001583]

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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diguanylate cyclase domain-containing protein [Phascolarctobacterium faecium]
diguanylate cyclase domain-containing protein [Phascolarctobacterium faecium]
gi|1828043758|ref|WP_167457040.1|

Protein
PREDICTED: Homo sapiens ArfGAP with coiled-coil, ankyrin repeat and PH domains 3...
PREDICTED: Homo sapiens ArfGAP with coiled-coil, ankyrin repeat and PH domains 3 (ACAP3), transcript variant X2, mRNA
gi|2217263716|ref|XM_011540607.2|

Nucleotide
probable galacturonosyltransferase 10 [Capsella rubella]
probable galacturonosyltransferase 10 [Capsella rubella]
gi|565479522|ref|XP_006297401.1|

Protein
Loa loa glycosyl transferase mRNA
Loa loa glycosyl transferase mRNA
gi|1158589161|ref|XM_020447262.1|

Nucleotide
Homo sapiens archaelysin family metallopeptidase 2 (AMZ2), transcript variant 17...
Homo sapiens archaelysin family metallopeptidase 2 (AMZ2), transcript variant 17, mRNA
gi|1890266949|ref|NM_001346479.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000827698	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 27, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30050099, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000827698

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 27, 2022)

germline

clinical testing

PubMed (2)
[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

Metabolome-guided genomics to identify pathogenic variants in isocitrate dehydrogenase, fumarate hydratase, and succinate dehydrogenase genes in pheochromocytoma and paraganglioma.

Richter S, Gieldon L, Pang Y, Peitzsch M, Huynh T, Leton R, Viana B, Ercolino T, Mangelis A, Rapizzi E, Menschikowski M, Aust D, Kroiss M, Beuschlein F, Gudziol V, Timmers HJ, Lenders J, Mannelli M, Cascon A, Pacak K, Robledo M, Eisenhofer G, et al.

Genet Med. 2019 Mar;21(3):705-717. doi: 10.1038/s41436-018-0106-5. Epub 2018 Jul 27.

PubMed [citation]

PMID:: 30050099
PMCID:: PMC6353556

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000827698.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 576498). This missense change has been observed in individual(s) with clinical features of SDHC-related conditions (PMID: 30050099). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 67 of the SDHC protein (p.Met67Thr).

#	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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