ClinVar Miner

Submissions for variant NM_014363.6(SACS):c.13027G>A (p.Glu4343Lys)

gnomAD frequency: 0.00008  dbSNP: rs749383532
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000593745 SCV000709513 uncertain significance not provided 2017-06-29 criteria provided, single submitter clinical testing
Counsyl RCV000671806 SCV000796827 uncertain significance Charlevoix-Saguenay spastic ataxia 2018-01-08 criteria provided, single submitter clinical testing
GeneDx RCV000593745 SCV001986228 uncertain significance not provided 2019-08-07 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 20876471, 29203718)
Genome-Nilou Lab RCV000671806 SCV002027680 uncertain significance Charlevoix-Saguenay spastic ataxia 2021-09-05 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002232237 SCV002511800 uncertain significance not specified 2022-04-08 criteria provided, single submitter clinical testing Variant summary: SACS c.13027G>A (p.Glu4343Lys) results in a conservative amino acid change located in the DnaJ domain (IPR001623) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6.4e-05 in 250148 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in SACS causing Autosomal Recessive Spastic Ataxia Of Charlevoix-Saguenay (6.4e-05 vs 0.0079), allowing no conclusion about variant significance. c.13027G>A has been reported in the literature in one individual with some clinical features of Autosomal Recessive Spastic Ataxia Of Charlevoix-Saguenay (ARSACS), however this individual had very late onset cerebellar atrophy and gait impairments with no signs of neuropathy (Baets_2010). This report does not provide unequivocal conclusions about association of the variant with Autosomal Recessive Spastic Ataxia Of Charlevoix-Saguenay. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submitters have assessed the variant since 2014: all four classified the variant as of uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV002532677 SCV003513662 benign Spastic paraplegia 2024-01-31 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000671806 SCV003820609 uncertain significance Charlevoix-Saguenay spastic ataxia 2019-05-11 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.