ClinVar Miner

Submissions for variant NM_001005373.4(LRSAM1):c.1405C>T (p.Arg469Trp)

gnomAD frequency: 0.00011  dbSNP: rs376468970
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 RCV001070341 SCV001235564 uncertain significance Charcot-Marie-Tooth disease axonal type 2P 2023-02-01 criteria provided, single submitter clinical testing 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. 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 LRSAM1 protein function. ClinVar contains an entry for this variant (Variation ID: 863385). This variant has not been reported in the literature in individuals affected with LRSAM1-related conditions. This variant is present in population databases (rs376468970, gnomAD 0.03%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 469 of the LRSAM1 protein (p.Arg469Trp).
GeneDx RCV001560780 SCV001783253 likely benign not provided 2021-07-29 criteria provided, single submitter clinical testing
Ambry Genetics RCV002393337 SCV002698890 uncertain significance Inborn genetic diseases 2022-03-02 criteria provided, single submitter clinical testing The p.R469W variant (also known as c.1405C>T), located in coding exon 17 of the LRSAM1 gene, results from a C to T substitution at nucleotide position 1405. The arginine at codon 469 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the supporting evidence, this variant is unlikely to be causative of autosomal dominant Charcot-Marie-Tooth disease; however, its contribution to the development of autosomal recessive Charcot-Marie-Tooth disease is uncertain.

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.