ClinVar Miner

Submissions for variant NM_198586.3(NHLRC1):c.874A>T (p.Thr292Ser)

gnomAD frequency: 0.00030  dbSNP: rs200214191
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000687470 SCV000815035 uncertain significance Lafora disease 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 292 of the NHLRC1 protein (p.Thr292Ser). This variant is present in population databases (rs200214191, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with NHLRC1-related conditions. ClinVar contains an entry for this variant (Variation ID: 567398). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NHLRC1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV001566255 SCV001789746 uncertain significance not provided 2022-03-09 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002369837 SCV002685851 uncertain significance Inborn genetic diseases 2018-08-29 criteria provided, single submitter clinical testing The p.T292S variant (also known as c.874A>T), located in coding exon 1 of the NHLRC1 gene, results from an A to T substitution at nucleotide position 874. The threonine at codon 292 is replaced by serine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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.