VCV000004588.23 - ClinVar

NM_030777.4(SLC2A10):c.243C>G (p.Ser81Arg)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(9)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic/Likely pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_030777.4(SLC2A10):c.243C>G (p.Ser81Arg)

Variation ID: 4588 Accession: VCV000004588.23

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 20q13.12 20: 46725279 (GRCh38) [ NCBI UCSC ] 20: 45353918 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Oct 11, 2015	Oct 8, 2024	Mar 17, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_030777.4:c.243C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_110404.1:p.Ser81Arg	missense
NC_000020.11:g.46725279C>G
NC_000020.10:g.45353918C>G
NG_016284.1:g.20640C>G
	O95528:p.Ser81Arg

... more HGVS ... less HGVS

Protein change

S81R

Other names

Canonical SPDI

NC_000020.11:46725278:C:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA340266 UniProtKB: O95528#VAR_029535 OMIM: 606145.0004 dbSNP: rs80358230 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
SLC2A10		-	-	GRCh38 GRCh37	620	630

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Arterial tortuosity syndrome	Pathogenic/Likely pathogenic (7)	criteria provided, multiple submitters, no conflicts	Mar 17, 2024	RCV000004850.27
not provided	Pathogenic (1)	criteria provided, single submitter	Nov 27, 2023	RCV000498947.13
SLC2A10-related disorder	Pathogenic (1)	no assertion criteria provided	Mar 24, 2024	RCV003914808.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Jun 15, 2020)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Arterial tortuosity syndrome Affected status: yes Allele origin: unknown	Baylor Genetics Accession: SCV001521670.1 First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021	Comment: This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Likely pathogenic (Jan 01, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Arterial tortuosity syndrome Affected status: yes Allele origin: biparental	Provincial Medical Genetics Program of British Columbia, University of British Columbia Accession: SCV002320826.1 First in ClinVar: Apr 11, 2022 Last updated: Apr 11, 2022	Sex: female
Pathogenic (Feb 16, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Arterial tortuosity syndrome Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000952040.4 First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024	Publications: PubMed (2) PubMed: 16550171‚ 18565096 Comment: This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 81 of the SLC2A10 protein (p.Ser81Arg). … (more) This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 81 of the SLC2A10 protein (p.Ser81Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with arterial tortuosity syndrome (PMID: 16550171, 18565096). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 4588). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SLC2A10 protein function. For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Mar 17, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Arterial tortuosity syndrome Affected status: unknown Allele origin: germline	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center Accession: SCV004805143.2 First in ClinVar: Mar 30, 2024 Last updated: Apr 06, 2024
Pathogenic (Nov 27, 2023)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000589588.6 First in ClinVar: Aug 20, 2017 Last updated: Sep 16, 2024	Comment: Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein … (more) Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31203799, 34426522, 16550171, 24123366, 25373504, 30090112, 18774132, 31625567, 35302653, 36011280, 18565096) (less)
Likely pathogenic (Sep 26, 2019)	no assertion criteria provided Method: clinical testing	Arterial tortuosity syndrome Affected status: yes Allele origin: germline	Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City Accession: SCV001133152.1 First in ClinVar: Jan 06, 2020 Last updated: Jan 06, 2020
Pathogenic (Aug 01, 2008)	no assertion criteria provided Method: literature only	ARTERIAL TORTUOSITY SYNDROME Affected status: not provided Allele origin: germline	OMIM Accession: SCV000025026.4 First in ClinVar: Apr 04, 2013 Last updated: Jun 02, 2024	Publications: PubMed (3) PubMed: 16550171‚ 18565096‚ 12801113 Comment on evidence: In 2 Middle Eastern families with arterial tortuosity syndrome (ATORS; 208050), 1 with 6 affected sibs and another with 2 affected sibs, Coucke et al. … (more) In 2 Middle Eastern families with arterial tortuosity syndrome (ATORS; 208050), 1 with 6 affected sibs and another with 2 affected sibs, Coucke et al. (2006) identified a homozygous mutation, 243C-G, in the SLC2A10 gene. The mutation resulted in a ser81-to-arg (S81R) amino acid substitution. Affected individuals shared a common haplotype, indicating a founder mutation in these families. Faiyaz-Ul-Haque et al. (2008) identified a homozygous S81R mutation in affected members of 10 Qatari families with arterial tortuosity syndrome. The substitution occurs in the third transmembrane domain of the SLC2A10 protein. Eight of the families belonged to a large consanguineous kindred that was part of an extended Bedouin tribe originally reported as having a unique form of Ehlers-Danlos syndrome (Abdul Wahab et al., 2003). (less)
Pathogenic (Mar 24, 2024)	no assertion criteria provided Method: clinical testing	SLC2A10-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004728776.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: The SLC2A10 c.243C>G variant is predicted to result in the amino acid substitution p.Ser81Arg. This variant has been reported to be pathogenic for arterial tortuosity … (more) The SLC2A10 c.243C>G variant is predicted to result in the amino acid substitution p.Ser81Arg. This variant has been reported to be pathogenic for arterial tortuosity syndrome (Coucke et al. 2006. PubMed ID: 16550171; Rodriguez-Flores et al. 2014. PubMed ID: 24123366; Faiyaz-Ul-Haque et al. 2009. PubMed ID: 18774132). This variant has not been reported in a large population database, indicating this variant is rare. This variant is interpreted as pathogenic. (less)
not provided (-)	no classification provided Method: literature only	Arterial tortuosity syndrome Affected status: yes Allele origin: germline	GeneReviews Accession: SCV000195645.2 First in ClinVar: Oct 11, 2015 Last updated: Oct 01, 2022	Publications: PubMed (3) PubMed: 16550171‚ 18774132‚ 18565096 BookShelf: NBK253404 BookShelf: NBK253404 Geographic origin: Middle Eastern

Comment:

This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 81 of the SLC2A10 protein (p.Ser81Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with arterial tortuosity syndrome (PMID: 16550171, 18565096). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 4588). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SLC2A10 protein function. For these reasons, this variant has been classified as Pathogenic.

Comment:

Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31203799, 34426522, 16550171, 24123366, 25373504, 30090112, 18774132, 31625567, 35302653, 36011280, 18565096)

Comment:

The SLC2A10 c.243C>G variant is predicted to result in the amino acid substitution p.Ser81Arg. This variant has been reported to be pathogenic for arterial tortuosity syndrome (Coucke et al. 2006. PubMed ID: 16550171; Rodriguez-Flores et al. 2014. PubMed ID: 24123366; Faiyaz-Ul-Haque et al. 2009. PubMed ID: 18774132). This variant has not been reported in a large population database, indicating this variant is rare. This variant is interpreted as pathogenic.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Arterial Tortuosity Syndrome.	Adam MP	-	2023	PMID: 25392904
A novel missense and a recurrent mutation in SLC2A10 gene of patients affected with arterial tortuosity syndrome.	Faiyaz-Ul-Haque M	Atherosclerosis	2009	PMID: 18774132
Identification of a p.Ser81Arg encoding mutation in SLC2A10 gene of arterial tortuosity syndrome patients from 10 Qatari families.	Faiyaz-Ul-Haque M	Clinical genetics	2008	PMID: 18565096
Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome.	Coucke PJ	Nature genetics	2006	PMID: 16550171
A new type of Ehlers-Danlos syndrome associated with tortuous systemic arteries in a large kindred from Qatar.	Abdul Wahab A	Acta paediatrica (Oslo, Norway : 1992)	2003	PMID: 12801113

Text-mined citations for rs80358230 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 10, 2024

ClinVar Genomic variation as it relates to human health

NM_030777.4(SLC2A10):c.243C>G (p.Ser81Arg)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs80358230 ...