NM_003000.3(SDHB):c.529C>T (p.Arg177Cys) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jun 25, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000757752.14

Allele description [Variation Report for NM_003000.3(SDHB):c.529C>T (p.Arg177Cys)]

NM_003000.3(SDHB):c.529C>T (p.Arg177Cys)

Gene:

SDHB:succinate dehydrogenase complex iron sulfur subunit B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.13

Genomic location:

Preferred name:

NM_003000.3(SDHB):c.529C>T (p.Arg177Cys)

HGVS:

NC_000001.11:g.17027760G>A
NG_012340.1:g.31411C>T
NM_003000.3:c.529C>TMANE SELECT
NP_002991.2:p.Arg177Cys
NP_002991.2:p.Arg177Cys
LRG_316t1:c.529C>T
LRG_316:g.31411C>T
LRG_316p1:p.Arg177Cys
NC_000001.10:g.17354255G>A
NM_003000.2:c.529C>T

Protein change:

R177C

Links:

dbSNP: rs149091125

NCBI 1000 Genomes Browser:

rs149091125

Molecular consequence:

NM_003000.3:c.529C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000886096	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	Uncertain significance (Feb 8, 2018)	germline	clinical testing	Citation Link,
SCV001784780	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jun 25, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000886096

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)

Uncertain significance
(Feb 8, 2018)

germline

clinical testing

Citation Link,

SCV001784780

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Jun 25, 2024)

germline

clinical testing

Citation Link

Help

Summary from all submissions

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

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000886096.1

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

Description

The SDHB c.529C>T; p.Arg177Cys variant (rs149091125), to our knowledge, is not reported in the medical literature, but it is classified as a variant of uncertain significance in ClinVar (Variant ID: 412469). This variant is also found in the non-Finnish European population with an allele frequency of 0.0036% (4/111,654 alleles) in the Genome Aggregation Database. The arginine at codon 177 is highly conserved considering 14 species up to bakerâ€™s yeast (Alamut software v2.10.0), and computational analyses predict that this variant affects the structure/function of the SDHB protein (SIFT: damaging, PolyPhen2: probably damaging). Based on the available information, the clinical significance of the p.Arg177Cys variant is uncertain at this time.

#	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

From GeneDx, SCV001784780.2

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

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.

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

Last Updated: Oct 8, 2024

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