ClinVar Miner

Submissions for variant NM_138361.5(LRSAM1):c.1781G>A (p.Arg594His) (rs537838691)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000726183 SCV000342717 uncertain significance not provided 2016-06-16 criteria provided, single submitter clinical testing
GeneDx RCV000726183 SCV000621517 uncertain significance not provided 2017-10-16 criteria provided, single submitter clinical testing The R594H variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R594H variant is observed in 3/34,406 (0.009%) alleles from individuals of Latino background (Lek et al., 2016). This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, the R594H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Molecular Genetics Laboratory,London Health Sciences Centre RCV001173640 SCV001336742 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Invitae RCV001224409 SCV001396601 uncertain significance Charcot-Marie-Tooth disease type 2P 2020-04-23 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 594 of the LRSAM1 protein (p.Arg594His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs537838691, ExAC 0.03%). This variant has not been reported in the literature in individuals with LRSAM1-related conditions. ClinVar contains an entry for this variant (Variation ID: 288562). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). 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.

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.