NM_003001.5(SDHC):c.367C>T (p.Pro123Ser) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 21, 2023
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:: RCV001759753.6

Allele description [Variation Report for NM_003001.5(SDHC):c.367C>T (p.Pro123Ser)]

NM_003001.5(SDHC):c.367C>T (p.Pro123Ser)

Gene:

SDHC:succinate dehydrogenase complex subunit C [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q23.3

Genomic location:

Preferred name:

NM_003001.5(SDHC):c.367C>T (p.Pro123Ser)

HGVS:

NC_000001.11:g.161356802C>T
NG_012767.1:g.47427C>T
NM_001035511.3:c.242-5527C>T
NM_001035512.3:c.265C>T
NM_001035513.3:c.208C>T
NM_001278172.3:c.140-5527C>T
NM_001407115.1:c.487C>T
NM_001407116.1:c.310C>T
NM_001407117.1:c.304C>T
NM_001407118.1:c.259C>T
NM_001407119.1:c.256C>T
NM_001407120.1:c.256C>T
NM_001407121.1:c.185-5527C>T
NM_003001.5:c.367C>TMANE SELECT
NP_001030589.1:p.Pro89Ser
NP_001030590.1:p.Pro70Ser
NP_001394044.1:p.Pro163Ser
NP_001394045.1:p.Pro104Ser
NP_001394046.1:p.Pro102Ser
NP_001394047.1:p.Pro87Ser
NP_001394048.1:p.Pro86Ser
NP_001394049.1:p.Pro86Ser
NP_002992.1:p.Pro123Ser
NP_002992.1:p.Pro123Ser
LRG_317t1:c.367C>T
LRG_317:g.47427C>T
LRG_317p1:p.Pro123Ser
NC_000001.10:g.161326592C>T
NM_003001.3:c.367C>T
NR_103459.3:n.419C>T

Protein change:

P102S

Links:

dbSNP: rs773039986

NCBI 1000 Genomes Browser:

rs773039986

Molecular consequence:

NM_001035511.3:c.242-5527C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001278172.3:c.140-5527C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001407121.1:c.185-5527C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001035512.3:c.265C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001035513.3:c.208C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407115.1:c.487C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407116.1:c.310C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407117.1:c.304C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407118.1:c.259C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407119.1:c.256C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407120.1:c.256C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003001.5:c.367C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_103459.3:n.419C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV001985289	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Sep 3, 2019)	germline	clinical testing	Citation Link,
SCV002046842	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Sep 21, 2023)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22829200, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001985289

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Sep 3, 2019)

germline

clinical testing

Citation Link,

SCV002046842

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Sep 21, 2023)

unknown

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	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Vitamin E protects against lipid peroxidation and rescues tumorigenic phenotypes in cowden/cowden-like patient-derived lymphoblast cells with germline SDHx variants.

Ni Y, Eng C.

Clin Cancer Res. 2012 Sep 15;18(18):4954-61. Epub 2012 Jul 24.

PubMed [citation]

PMID:: 22829200
PMCID:: PMC3445717

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Details of each submission

From GeneDx, SCV001985289.2

#	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 a significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Observed in individuals with features of Cowden syndrome (Ni 2012); This variant is associated with the following publications: (PMID: 22829200)

#	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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV002046842.2

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

Description

In the published literature, this variant has been reported in an individual with Cowden syndrome or Cowden-like syndrome (PMID: 22829200 (2012)). The frequency of this variant in the general population, 0.000047 (6/126772 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant.

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

Last Updated: Sep 29, 2024

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