NM_003000.3(SDHB):c.739A>G (p.Met247Val) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Feb 14, 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:: RCV000575911.12

Allele description [Variation Report for NM_003000.3(SDHB):c.739A>G (p.Met247Val)]

NM_003000.3(SDHB):c.739A>G (p.Met247Val)

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.739A>G (p.Met247Val)

HGVS:

NC_000001.11:g.17022634T>C
NG_012340.1:g.36537A>G
NM_003000.3:c.739A>GMANE SELECT
NP_002991.2:p.Met247Val
NP_002991.2:p.Met247Val
LRG_316t1:c.739A>G
LRG_316:g.36537A>G
LRG_316p1:p.Met247Val
NC_000001.10:g.17349129T>C
NM_003000.2:c.739A>G

Protein change:

M247V

Links:

dbSNP: rs200896502

NCBI 1000 Genomes Browser:

rs200896502

Molecular consequence:

NM_003000.3:c.739A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000675066	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Feb 14, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV002527091	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Uncertain significance (Aug 10, 2021)	germline	curation	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000675066

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Feb 14, 2024)

germline

clinical testing

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

Citation Link,

SCV002527091

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Uncertain significance
(Aug 10, 2021)

germline

curation

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

Citation Link

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, curation

Citations

PubMed

Clinical and Molecular Assessment of Patients with Lynch Syndrome and Sarcomas Underpinning the Association with MSH2 Germline Pathogenic Variants.

de Angelis de Carvalho N, Niitsuma BN, Kozak VN, Costa FD, de Macedo MP, Kupper BEC, Silva MLG, Formiga MN, Volc SM, Aguiar Junior S, Palmero EI, Casali-da-Rocha JC, Carraro DM, Torrezan GT.

Cancers (Basel). 2020 Jul 9;12(7). doi:pii: E1848. 10.3390/cancers12071848.

PubMed [citation]

PMID:: 32659967
PMCID:: PMC7408879

Details of each submission

From Ambry Genetics, SCV000675066.5

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

Description

The p.M247V variant (also known as c.739A>G), located in coding exon 7 of the SDHB gene, results from an A to G substitution at nucleotide position 739. The methionine at codon 247 is replaced by valine, an amino acid with highly similar properties. In one study, this alteration was identified in a female patient diagnosed with high-grade vaginal fusocellular sarcoma and endometrial adenocarcinoma (de Angelis de Carvalho N et al. Cancers (Basel), 2020 Jul;12:). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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 Sema4, Sema4, SCV002527091.1

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

#	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: Jun 29, 2024

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