NM_003002.4(SDHD):c.20T>A (p.Leu7Gln) AND multiple conditions

delete

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 29, 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:: RCV001339445.1

Allele description

NM_003002.4(SDHD):c.20T>A (p.Leu7Gln)

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.20T>A (p.Leu7Gln)

HGVS:

NC_000011.10:g.112086927T>A
NG_012337.3:g.5081T>A
NG_033145.1:g.4872A>T
NM_001276503.2:c.20T>A
NM_001276504.2:c.20T>A
NM_001276506.2:c.20T>A
NM_003002.4:c.20T>AMANE SELECT
NP_001263432.1:p.Leu7Gln
NP_001263433.1:p.Leu7Gln
NP_001263435.1:p.Leu7Gln
NP_002993.1:p.Leu7Gln
LRG_9t1:c.20T>A
LRG_9:g.5081T>A
LRG_9p1:p.Leu7Gln
NC_000011.9:g.111957651T>A
NR_077060.2:n.55T>A

Protein change:

L7Q

Links:

dbSNP: rs1865619523

NCBI 1000 Genomes Browser:

rs1865619523

Molecular consequence:

NM_001276503.2:c.20T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276504.2:c.20T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276506.2:c.20T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003002.4:c.20T>A - missense variant - [Sequence Ontology: SO:0001583]
NR_077060.2:n.55T>A - 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 1
Synonyms:: Paragangliomata; Glomus tumors familial 1; Paraganglioma - glomus jugulare; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008192; MedGen: C3494181; Orphanet: 29072; OMIM: 168000

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001533188	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 29, 2020)	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

SCV001533188

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 29, 2020)

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001533188.1

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

Description

This sequence change replaces leucine with glutamine at codon 7 of the SDHD protein (p.Leu7Gln). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SDHD-related conditions. 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 not expected to disrupt SDHD protein function. 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.

#	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: Apr 23, 2022

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