ClinVar Miner

Submissions for variant NM_001271208.2(NEB):c.25472C>T (p.Thr8491Met) (rs78592085)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000724204 SCV000226194 uncertain significance not provided 2014-11-20 criteria provided, single submitter clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000202808 SCV000257875 uncertain significance not specified 2015-07-01 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000202808 SCV000307331 likely benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001080816 SCV000416806 uncertain significance Nemaline myopathy 2 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV000202808 SCV000491010 uncertain significance not specified 2016-12-02 criteria provided, single submitter clinical testing The T8491M variants in the NEB gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. While not present in the homozygous state, the NHLBI Exome Sequencing Project reports T8491M was observed in 22/8232 (0.3%) alleles from individuals of European American background and the 1000 Genomes Project reports this variant was observed in 2/214 (0.9%) alleles from individuals of Italian ancestry, indicating it may be a rare variant in these populations. The T8491M variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret T8491M as a variant of uncertain significance.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000415163 SCV000492765 uncertain significance Congenital muscular dystrophy; Muscle weakness 2014-05-21 criteria provided, single submitter clinical testing
Invitae RCV001080816 SCV000640756 likely benign Nemaline myopathy 2 2019-12-31 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001080816 SCV001368244 uncertain significance Nemaline myopathy 2 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance.
Natera, Inc. RCV001080816 SCV001454422 likely benign Nemaline myopathy 2 2020-01-13 no assertion criteria provided 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.