NM_003002.4(SDHD):c.389C>G (p.Ala130Gly) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 25, 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:: RCV001861019.6

Allele description [Variation Report for NM_003002.4(SDHD):c.389C>G (p.Ala130Gly)]

NM_003002.4(SDHD):c.389C>G (p.Ala130Gly)

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.389C>G (p.Ala130Gly)

HGVS:

NC_000011.10:g.112094879C>G
NG_012337.3:g.13033C>G
NM_001276503.2:c.244C>G
NM_001276504.2:c.272C>G
NM_001276506.2:c.*87C>G
NM_003002.4:c.389C>GMANE SELECT
NP_001263432.1:p.His82Asp
NP_001263433.1:p.Ala91Gly
NP_002993.1:p.Ala130Gly
LRG_9t1:c.389C>G
LRG_9:g.13033C>G
LRG_9p1:p.Ala130Gly
NC_000011.9:g.111965603C>G
NC_000011.9:g.111965603C>G
NM_003002.2:c.389C>G
NR_077060.2:n.478C>G

Protein change:

A130G

Links:

dbSNP: rs1049692537

NCBI 1000 Genomes Browser:

rs1049692537

Molecular consequence:

NM_001276506.2:c.*87C>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001276503.2:c.244C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276504.2:c.272C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_003002.4:c.389C>G - missense variant - [Sequence Ontology: SO:0001583]
NR_077060.2:n.478C>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
Identifiers:: MedGen: C1868633

Name:: Cowden syndrome 3 (CWS3)
Identifiers:: MONDO: MONDO:0014045; MedGen: CN166604; Orphanet: 201

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Mus musculus mitogen-activated protein kinase kinase 3, mRNA (cDNA clone MGC:591...
Mus musculus mitogen-activated protein kinase kinase 3, mRNA (cDNA clone MGC:5915 IMAGE:3497714), complete cds
gi|13938622|gb|BC007467.1|

Nucleotide
protein YhfH [Bacillus subtilis]
protein YhfH [Bacillus subtilis]
gi|2504824483|ref|WP_282297299.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002221999	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 25, 2023)	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

SCV002221999

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 25, 2023)

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, SCV002221999.3

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

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. 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. ClinVar contains an entry for this variant (Variation ID: 824350). This variant has not been reported in the literature in individuals affected with SDHD-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 130 of the SDHD protein (p.Ala130Gly).

#	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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