NM_030777.4(SLC2A10):c.685C>T (p.Arg229Ter) AND Arterial tortuosity syndrome

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Dec 11, 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:: RCV000202510.19

Allele description [Variation Report for NM_030777.4(SLC2A10):c.685C>T (p.Arg229Ter)]

NM_030777.4(SLC2A10):c.685C>T (p.Arg229Ter)

Gene:

SLC2A10:solute carrier family 2 member 10 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

20q13.12

Genomic location:

Preferred name:

NM_030777.4(SLC2A10):c.685C>T (p.Arg229Ter)

HGVS:

NC_000020.11:g.46725721C>T
NG_016284.1:g.21082C>T
NM_030777.4:c.685C>TMANE SELECT
NP_110404.1:p.Arg229Ter
NC_000020.10:g.45354360C>T
NM_030777.3:c.685C>T

Protein change:

R229*

Links:

dbSNP: rs756457861

NCBI 1000 Genomes Browser:

rs756457861

Molecular consequence:

NM_030777.4:c.685C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Arterial tortuosity syndrome (ATORS)
Identifiers:: MONDO: MONDO:0008818; MedGen: C1859726; Orphanet: 3342; OMIM: 208050

Recent activity

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SRX8142330 (1)
SRA
BJ035220 NIBB Mochii normalized Xenopus neurula library Xenopus laevis cDNA clon...
BJ035220 NIBB Mochii normalized Xenopus neurula library Xenopus laevis cDNA clone XL021g06 5', mRNA sequence
gi|17414473|gnl|dbEST|10500747|dbj| 220.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000195648	GeneReviews	no classification provided	not provided	germline	literature only	PubMed (3) [See all records that cite these PMIDs] 17935213, 19781076, 19622975
SCV000549138	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 11, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 22488877, 23494979, 17935213, 19622975, 19781076, 28492532
SCV004847692	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 16, 2019)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 28152038, 30425910, 17935213, 19622975, 19781076, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000195648

GeneReviews

no classification provided

not provided

germline

literature only

PubMed (3)
[See all records that cite these PMIDs]

SCV000549138

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 11, 2023)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

SCV004847692

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 16, 2019)

germline

clinical testing

PubMed (6)
[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	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Adult presentation of arterial tortuosity syndrome in a 51-year-old woman with a novel homozygous c.1411+1G>A mutation in the SLC2A10 gene.

Castori M, Ritelli M, Zoppi N, Molisso L, Chiarelli N, Zaccagna F, Grammatico P, Colombi M.

Am J Med Genet A. 2012 May;158A(5):1164-9. doi: 10.1002/ajmg.a.35266. Epub 2012 Apr 9.

PubMed [citation]

PMID:: 22488877

Artery tortuosity syndrome exhibiting early-onset emphysema with novel compound heterozygous SLC2A10 mutations.

Takahashi Y, Fujii K, Yoshida A, Morisaki H, Kohno Y, Morisaki T.

Am J Med Genet A. 2013 Apr;161A(4):856-9. doi: 10.1002/ajmg.a.35776. Epub 2013 Mar 12.

PubMed [citation]

PMID:: 23494979

See all PubMed Citations (9)

Details of each submission

From GeneReviews, SCV000195648.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (3)

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000549138.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change creates a premature translational stop signal (p.Arg229*) in the SLC2A10 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC2A10 are known to be pathogenic (PMID: 17935213, 22488877, 23494979). This variant is present in population databases (rs756457861, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with arterial tortuosity syndrome (PMID: 17935213, 19622975, 19781076). ClinVar contains an entry for this variant (Variation ID: 161096). For these reasons, this variant has been classified as Pathogenic.

#	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 Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004847692.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

The p.Arg229X variant in SLC2A10 has been reported in 3 homozygous and 1 compound heterozygous individuals with arterial tortuosity syndrome (Allen 2009, Callewaert 2008, Kocova 2018, Ritelli 2009). It has also been identified in 0.0035% (4/113394) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org) and has been reported in ClinVar (Variation ID 161096). This nonsense variant leads to a premature termination codon at position 229, which is predicted to lead to a truncated or absent protein. Loss of function of the SLC2A10 gene is an established disease mechanism in autosomal recessive arterial tortuosity syndrome. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive arterial tortuosity syndrome. ACMG/AMP Criteria applied: PVS1, PM3_Strong, PM2_Supporting.

#	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: Nov 10, 2024

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