NM_003000.3(SDHB):c.744C>G (p.Asn248Lys) AND Paraganglioma

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 11, 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:: RCV002250641.3

Allele description [Variation Report for NM_003000.3(SDHB):c.744C>G (p.Asn248Lys)]

NM_003000.3(SDHB):c.744C>G (p.Asn248Lys)

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.744C>G (p.Asn248Lys)

HGVS:

NC_000001.11:g.17022629G>C
NG_012340.1:g.36542C>G
NM_003000.3:c.744C>GMANE SELECT
NP_002991.2:p.Asn248Lys
NP_002991.2:p.Asn248Lys
LRG_316t1:c.744C>G
LRG_316:g.36542C>G
LRG_316p1:p.Asn248Lys
NC_000001.10:g.17349124G>C
NM_003000.2:c.744C>G

Protein change:

N248K

Links:

dbSNP: rs1131691058

NCBI 1000 Genomes Browser:

rs1131691058

Molecular consequence:

NM_003000.3:c.744C>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Paraganglioma
Synonyms:: Carotid body tumor
Identifiers:: MONDO: MONDO:0000448; MedGen: C0030421; OMIM: PS168000; Human Phenotype Ontology: HP:0002668

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002521910	Cancer Variant Interpretation Group UK, Institute of Cancer Research, London	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 11, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 34906457, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002521910

Cancer Variant Interpretation Group UK, Institute of Cancer Research, London

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 11, 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	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Quantifying evidence toward pathogenicity for rare phenotypes: The case of succinate dehydrogenase genes, SDHB and SDHD.

Garrett A, Loveday C, King L, Butler S, Robinson R, Horton C, Yussuf A, Choi S, Torr B, Durkie M, Burghel GJ, Drummond J, Berry I, Wallace A, Callaway A, Eccles D, Tischkowitz M, Tatton-Brown K, Snape K, McVeigh T, Izatt L, Woodward ER, et al.

Genet Med. 2022 Jan;24(1):41-50. doi: 10.1016/j.gim.2021.08.004. Epub 2021 Nov 30.

PubMed [citation]

PMID:: 34906457
PMCID:: PMC8759765

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Cancer Variant Interpretation Group UK, Institute of Cancer Research, London, SCV002521910.1

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

Description

Data included in classification: Absent from gnomAD (PM2_mod) Phenotype data: UK family #1: Observed in proband with bilateral head and neck paragangliomas (PP4_mod) Revel score >0.7 (0.866) (PP3_sup) Within “hot region” for SDHB as defined in Garrett et al. 2021 (https://doi.org/10.1016/j.gim.2021.08.004). (amino acids 177-260) (PM1_mod) Data not included in classification: Observed in Garrett et al. 2021 (https://doi.org/10.1016/j.gim.2021.08.004). 1/6118 cases (likely same proband from UK family #1) Crystal structure of mitochondrial respiratory membrane protein complex II.Sun F, Huo X, Zhai Y, Wang A, Xu J, Su D, Bartlam M, Rao Z.Cell. 2005 Jul 1;121(7):1043-57.PMID:15989954

#	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		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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