ClinVar Miner

Submissions for variant NM_014363.6(SACS):c.1373C>T (p.Thr458Ile) (rs61729954)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000676372 SCV000333837 uncertain significance not provided 2015-08-13 criteria provided, single submitter clinical testing
Invitae RCV000676372 SCV000562824 likely benign not provided 2019-03-05 criteria provided, single submitter clinical testing
GeneDx RCV000335849 SCV000565514 uncertain significance not specified 2016-10-18 criteria provided, single submitter clinical testing The T458I variant in the SACS gene was initially reported in two unrelated individuals with anatypical presentation of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS).However, as this variant was also observed with a frequency of 0.40% (14/3500) in controlchromosomes, the authors interpreted T458I as a variant of unknown significance (Synofzik et al.,2013). The T458I variant has also been reported in the compound heterozygous state in an individualwith ARSCAS who harbored a 1.5 Mb deletion which encompassed the entire opposite SACS allele(Romano et al., 2013). In addition, the T458I variant has been observed along with another SACSmissense variant in two individuals with progressive myoclonus epilepsy (Muona et al., 2015;Nascimento et al., 2016). Although not present in the homozygous state, the NHLBI ESP ExomeSequencing Project reports T458I was observed in 29/8600 (0.34%) alleles from individuals ofEuropean American background. The T458I variant is a non-conservative amino acid substitution,which occurs at a position that is conserved across species. In silico analysis predicts this variant isprobably damaging to the protein structure/function. Given the available data, we interpret T458I as avariant of uncertain significance.
Unit for Genetic & Epidemiological Research on Neurological Disorders,Instituto de Investigação e Inovação em Saúde RCV000516147 SCV000574488 uncertain significance Hereditary spastic paraplegia 2017-03-07 criteria provided, single submitter research
Athena Diagnostics Inc RCV000676372 SCV000614939 benign not provided 2019-02-06 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000603816 SCV000744372 uncertain significance Spastic ataxia Charlevoix-Saguenay type 2015-09-21 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000676372 SCV001148952 uncertain significance not provided 2018-11-01 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000603816 SCV000733512 uncertain significance Spastic ataxia Charlevoix-Saguenay type no assertion criteria provided clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000676372 SCV000802148 uncertain significance not provided 2016-02-19 no assertion criteria provided clinical testing

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