ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.329G>A (p.Arg110His)

gnomAD frequency: 0.00005  dbSNP: rs556237236
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
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000626177 SCV000746813 likely pathogenic Dilated cardiomyopathy 1A 2020-05-03 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001186690 SCV001353242 uncertain significance Cardiomyopathy 2020-10-22 criteria provided, single submitter clinical testing This missense variant replaces arginine with histidine at codon 110 of the lamin A/C proteins. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 13/242084 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The relatively high frequency of this variant in the general population suggests that this variant is unlikely to be disease-causing. However, additional studies are necessary to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Invitae RCV003106008 SCV003781248 uncertain significance Charcot-Marie-Tooth disease type 2 2023-08-02 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. Experimental studies have shown that this missense change does not substantially affect LMNA function (PMID: 34862408). 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 expected to disrupt LMNA protein function. ClinVar contains an entry for this variant (Variation ID: 522979). This variant has not been reported in the literature in individuals affected with LMNA-related conditions. This variant is present in population databases (rs556237236, gnomAD 0.04%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 110 of the LMNA protein (p.Arg110His).

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.