ClinVar Miner

Submissions for variant NM_001271208.2(NEB):c.24684G>C (p.Ser8228=) (rs202048855)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000814228 SCV000954629 pathogenic Nemaline myopathy 2 2019-09-06 criteria provided, single submitter clinical testing This sequence change affects codon 8228 of the NEB mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the NEB protein. This variant also falls at the last nucleotide of exon 175 of the NEB coding sequence, which is part of the consensus splice site for this exon. This variant is present in population databases (rs202048855, ExAC 0.05%). This variant has been observed in individual(s) with nemaline myopathy (PMID: 30467404). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 30467404). This variant disrupts the c..24684G nucleotide in the NEB gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 24725366, 29669168). This suggests that this nucleotide is clinically-significant, and that variants that disrupt this position are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Illumina Clinical Services Laboratory,Illumina RCV000814228 SCV001288665 uncertain significance Nemaline myopathy 2 2018-01-12 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.

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.