ClinVar Miner

Submissions for variant NM_030777.4(SLC2A10):c.1334del (p.Gly445fs) (rs587776600)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000197366 SCV000250733 pathogenic not provided 2018-05-21 criteria provided, single submitter clinical testing The c.1334delG variant in the SLC2A10 gene has been reported previously in the homozygous or compound heterozygous state in multiple unrelated families with arterial tortuosity syndrome (Coucke et al. 2006; Callewaert et al., 2008). This variant causes a frameshift starting with codon Glycine 445, changing it to a Glutamic acid, and creating a premature stop codon at position 40 of the new reading frame, denoted p.Gly445GlufsX40. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Although not present in the homozygous state, the c.1334delG variant is observed in 4/66740 (0.01%) alleles from individuals of non-Finnish European background,in the ExAC dataset (Lek et al., 2016). We interpret c.1334delG as a pathogenic variant.
Ambry Genetics RCV000243541 SCV000319330 pathogenic Cardiovascular phenotype 2016-06-16 criteria provided, single submitter clinical testing The c.1334delG pathogenic mutation, located in coding exon 3 of the SLC2A10 gene, results from a deletion of one nucleotide at nucleotide position 1334, causing a translational frameshift with a predicted alternate stop codon (<span style="background-color:initial">p.G445Efs*40)<span style="background-color:initial">. This mutation was reported in association with arterial tortuosity syndrome (ATS) in the homozygous state in an Italian family with consanguinity (<span style="background-color:initial">Coucke PJ et al. Nat Genet. 2006;38(4):452-7). This recurrent mutation, which is in the endofacial loop between TMD10 and TMD11, was also reported in four European families each in compound heterozygosity with another mutation (<span style="background-color:initial">Callewaert BL et al. Hum Mutat. 2008;29(1):150-8). <span style="background-color:initial">In addition to the clinical data presented in the literature, since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med.<span style="background-color:initial"> 2008;10:294).
Invitae RCV000004849 SCV001413726 pathogenic Arterial tortuosity syndrome 2020-10-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gly445Glufs*40) in the SLC2A10 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs758681965, ExAC 0.01%). This variant has been observed to segregate with autosomal recessive arterial tortuosity syndrome in several families (PMID: 16550171, 17935213), and has been reported in combination with another SLC2A10 variant in other affected individuals (PMID: 28726533,19781076). ClinVar contains an entry for this variant (Variation ID: 4587). Loss-of-function variants in SLC2A10 are known to be pathogenic (PMID: 17935213, 22488877, 23494979). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000004849 SCV000025025 pathogenic Arterial tortuosity syndrome 2008-01-01 no assertion criteria provided literature only
GeneReviews RCV000004849 SCV000195651 pathogenic Arterial tortuosity syndrome 2014-09-10 no assertion criteria provided literature only
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000004849 SCV000692260 pathogenic Arterial tortuosity syndrome 2017-05-24 no assertion criteria provided clinical testing

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