ClinVar Miner

Submissions for variant NM_015046.7(SETX):c.7417C>G (p.Leu2473Val)

gnomAD frequency: 0.00001  dbSNP: rs760196991
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000585562 SCV000693306 uncertain significance not provided 2017-08-01 criteria provided, single submitter clinical testing
GeneDx RCV000585562 SCV001998433 uncertain significance not provided 2020-05-07 criteria provided, single submitter clinical testing Reported as a single heterozygous variant in a patient with hereditary spastic paraplegia and the affected father (Elert-Dobkowska et al., 2019); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 30778698)
Labcorp Genetics (formerly Invitae), Labcorp RCV001860112 SCV002223846 benign Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 2023-07-07 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003233754 SCV003931744 uncertain significance Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 2023-02-08 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003233755 SCV003931755 uncertain significance Amyotrophic lateral sclerosis type 4 2023-02-08 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV003233755 SCV004047383 uncertain significance Amyotrophic lateral sclerosis type 4 criteria provided, single submitter clinical testing The missense variant c.7417C>G (p.Leu2473Val) in SETX gene has been reported in heterozygous state affected with Hereditary spastic paraplegia (ElertDobkowska E et al., 2019). The p.Asn541Asp variant has allele frequency 0.004% in the gnomAD exomes and novel in 1000 genome database. This variant has been reported to the ClinVar database as Uncertain Significance. The amino acid Leu at position 2473 is changed to a Val changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Leu2473Val in SETX is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance (VUS).
PreventionGenetics, part of Exact Sciences RCV004530633 SCV004108608 uncertain significance SETX-related disorder 2023-01-10 criteria provided, single submitter clinical testing The SETX c.7417C>G variant is predicted to result in the amino acid substitution p.Leu2473Val. This variant was reported as a variant of uncertain significance in an individual with spastic paraplegia and was inherited from a similarly affected father (Elert-Dobkowska et al 2019. PubMed ID: 30778698). This variant is reported in 0.026% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-135140243-G-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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