ClinVar Miner

Submissions for variant NM_014363.6(SACS):c.8393C>A (p.Pro2798Gln) (rs140551762)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000194652 SCV000248787 likely pathogenic Charlevoix-Saguenay spastic ataxia 2014-06-27 criteria provided, single submitter clinical testing
Invitae RCV000230214 SCV000289962 uncertain significance Spastic paraplegia 2019-12-26 criteria provided, single submitter clinical testing This sequence change replaces proline with glutamine at codon 2798 of the SACS protein (p.Pro2798Gln). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and glutamine. This variant is present in population databases (rs140551762, ExAC 0.3%). This variant has been reported in individuals affected with progressive myoclonus epilepsies (PMID: 25401298, 27433545) and with late-onset forms of autosomal recessive spastic ataxia of Charlevoix-Saguenay (PMID: 20876471). ClinVar contains an entry for this variant (Variation ID: 212115). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. It has been reported in both the population and affected individuals, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000513770 SCV000331577 uncertain significance not provided 2015-09-21 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000513770 SCV000610377 uncertain significance not provided 2017-06-20 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000513770 SCV000614988 likely benign not provided 2020-03-25 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000513770 SCV000780455 uncertain significance not provided 2021-06-01 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000513770 SCV000802133 uncertain significance not provided 2021-02-04 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000194652 SCV001266629 uncertain significance Charlevoix-Saguenay spastic ataxia 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Clinical Genetics Karolinska University Hospital,Karolinska University Hospital RCV000513770 SCV001450121 pathogenic not provided 2014-11-11 criteria provided, single submitter clinical testing
Baylor Genetics RCV000194652 SCV001529507 uncertain significance Charlevoix-Saguenay spastic ataxia 2018-07-24 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx RCV000513770 SCV001771583 likely benign not provided 2020-12-09 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 20876471, 25401298, 27433545, 23280630)
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000513770 SCV001739905 uncertain significance not provided no assertion criteria provided clinical testing

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