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NM_030777.4(SLC2A10):c.1309G>A (p.Glu437Lys) AND Arterial tortuosity syndrome

Germline classification:
Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:
Mar 29, 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:
RCV000202526.19

Allele description [Variation Report for NM_030777.4(SLC2A10):c.1309G>A (p.Glu437Lys)]

NM_030777.4(SLC2A10):c.1309G>A (p.Glu437Lys)

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.1309G>A (p.Glu437Lys)
HGVS:
  • NC_000020.11:g.46726884G>A
  • NG_016284.1:g.22245G>A
  • NM_030777.4:c.1309G>AMANE SELECT
  • NP_110404.1:p.Glu437Lys
  • NP_110404.1:p.Glu437Lys
  • NC_000020.10:g.45355523G>A
  • NM_030777.3:c.1309G>A
  • O95528:p.Glu437Lys
Protein change:
E437K
Links:
UniProtKB: O95528#VAR_042423; dbSNP: rs763220502
NCBI 1000 Genomes Browser:
rs763220502
Molecular consequence:
  • NM_030777.4:c.1309G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000195654GeneReviews
no classification provided
not providedgermlineliterature only

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

SCV000822280Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Jul 8, 2023)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV004808049Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Mar 29, 2024)
germlineclinical testing

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

SCV005062103Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Pathogenic
(Mar 8, 2024)
germlineclinical testing

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

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedliterature only
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Arterial Tortuosity Syndrome: homozygosity for two novel and one recurrent SLC2A10 missense mutations in three families with severe cardiopulmonary complications in infancy and a literature review.

Ritelli M, Chiarelli N, Dordoni C, Reffo E, Venturini M, Quinzani S, Monica MD, Scarano G, Santoro G, Russo MG, Calzavara-Pinton P, Milanesi O, Colombi M.

BMC Med Genet. 2014 Nov 6;15:122. doi: 10.1186/s12881-014-0122-5. Review.

PubMed [citation]
PMID:
25373504
PMCID:
PMC4412100

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818
See all PubMed Citations (6)

Details of each submission

From GeneReviews, SCV000195654.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000822280.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

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. This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 437 of the SLC2A10 protein (p.Glu437Lys). This variant is present in population databases (rs763220502, gnomAD 0.006%). This missense change has been observed in individual(s) with arterial tortuosity syndrome (PMID: 17163528, 17935213, 25373504). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 161100). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, SCV004808049.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005062103.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Variant summary: SLC2A10 c.1309G>A (p.Glu437Lys) results in a conservative amino acid change located in the Major facilitator superfamily domain (IPR020846) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251422 control chromosomes. c.1309G>A has been reported in the literature in multiple homozygous and compound heterozygous individuals affected with Arterial Tortuosity Syndrome (e.g. Beyens_2018, Callewaert_2008, Drera_2007). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 29323665, 17935213, 17163528). ClinVar contains an entry for this variant (Variation ID: 161100). Based on the evidence outlined above, the variant was classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 10, 2024