NM_003001.5(SDHC):c.196G>A (p.Ala66Thr) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 13, 2019
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:: RCV001041119.10

Allele description [Variation Report for NM_003001.5(SDHC):c.196G>A (p.Ala66Thr)]

NM_003001.5(SDHC):c.196G>A (p.Ala66Thr)

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.196G>A (p.Ala66Thr)

HGVS:

NC_000001.11:g.161340610G>A
NG_012767.1:g.31235G>A
NM_001035511.3:c.196G>A
NM_001035512.3:c.94G>A
NM_001035513.3:c.37G>A
NM_001278172.3:c.94G>A
NM_001407115.1:c.316G>A
NM_001407116.1:c.139G>A
NM_001407117.1:c.139G>A
NM_001407118.1:c.94G>A
NM_001407119.1:c.85G>A
NM_001407120.1:c.85G>A
NM_001407121.1:c.139G>A
NM_003001.5:c.196G>AMANE SELECT
NP_001030588.1:p.Ala66Thr
NP_001030588.1:p.Ala66Thr
NP_001030589.1:p.Ala32Thr
NP_001030589.1:p.Ala32Thr
NP_001030590.1:p.Ala13Thr
NP_001030590.1:p.Ala13Thr
NP_001265101.1:p.Ala32Thr
NP_001265101.1:p.Ala32Thr
NP_001394044.1:p.Ala106Thr
NP_001394045.1:p.Ala47Thr
NP_001394046.1:p.Ala47Thr
NP_001394047.1:p.Ala32Thr
NP_001394048.1:p.Ala29Thr
NP_001394049.1:p.Ala29Thr
NP_001394050.1:p.Ala47Thr
NP_002992.1:p.Ala66Thr
NP_002992.1:p.Ala66Thr
LRG_317t1:c.196G>A
LRG_317:g.31235G>A
LRG_317p1:p.Ala66Thr
NC_000001.10:g.161310400G>A
NM_001035511.2:c.196G>A
NM_001035512.2:c.94G>A
NM_001035513.2:c.37G>A
NM_001278172.2:c.94G>A
NM_003001.3:c.196G>A
NR_103459.2:n.248G>A
NR_103459.3:n.248G>A

Protein change:

A106T

Links:

dbSNP: rs1162090559

NCBI 1000 Genomes Browser:

rs1162090559

Molecular consequence:

NM_001035511.3:c.196G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001035512.3:c.94G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001035513.3:c.37G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001278172.3:c.94G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407115.1:c.316G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407116.1:c.139G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407117.1:c.139G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407118.1:c.94G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407119.1:c.85G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407120.1:c.85G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407121.1:c.139G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003001.5:c.196G>A - 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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NBB2001-086
NBB2001-086

biosample
LCP family protein [Streptococcus salivarius]
LCP family protein [Streptococcus salivarius]
gi|2575279551|ref|WP_309164731.1|

Protein
Pathogen: clinical or host-associated sample from Streptococcus agalactiae
Pathogen: clinical or host-associated sample from Streptococcus agalactiae

biosample
Streptococcus agalactiae strain ES-PW-088, whole genome shotgun sequencing proje...
Streptococcus agalactiae strain ES-PW-088, whole genome shotgun sequencing project
gi|825830330|gb|LCVN00000000.1|LCVN 000

Nucleotide
Streptococcus agalactiae strain SH2898, whole genome shotgun sequencing project
Streptococcus agalactiae strain SH2898, whole genome shotgun sequencing project
gi|825923417|gb|LDAL00000000.1|LDAL 000

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001204715	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 13, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001204715

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 13, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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, SCV001204715.5

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

Description

Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 has not been reported in the literature in individuals with SDHC-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with threonine at codon 66 of the SDHC protein (p.Ala66Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine.

#	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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