Submissions for variant NM_005572.4(LMNA):c.1712G>A (p.Arg571His)

gnomAD frequency: 0.00003  dbSNP: rs200917748

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000182349	SCV000234661	benign	not specified	2014-07-11	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Personalized Diabetes Medicine Program, University of Maryland School of Medicine	RCV000664076	SCV000787528	likely benign	Monogenic diabetes	2017-05-19	criteria provided, single submitter	research	ACMG Criteria:PP3 (4 predictors), BP4 (6 predictors), BP6 (GeneDx)
Color Diagnostics, LLC DBA Color Health	RCV000778037	SCV000914150	benign	Cardiomyopathy	2018-10-16	criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852591	SCV000995293	benign	Long QT syndrome	2018-05-26	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001852310	SCV002167285	uncertain significance	Charcot-Marie-Tooth disease type 2	2021-12-07	criteria provided, single submitter	clinical testing	The LMNA gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_005572.4, and corresponds to LMNA/NM_170707.3:c.1698+14G>A in the primary transcript. This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 571 of the LMNA protein (p.Arg571His). This variant is present in population databases (rs200917748, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with LMNA-related conditions. ClinVar contains an entry for this variant (Variation ID: 200928). This variant disrupts the p.Arg571 amino acid residue in LMNA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10580070, 28686329; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002464010	SCV002605293	uncertain significance	Primary dilated cardiomyopathy		criteria provided, single submitter	research	Potent mutations in LMNA gene can lead to structural alteration in skeletal and cardiac muscle by altering the structure of Lamin A and Lamin C. It is associated with dilated cardiomyopathy and skeletal muscle dystrophies. However no sufficient evidence is found to ascertain the role of this particular variant rs200917748, yet.
All of Us Research Program, National Institutes of Health	RCV002464010	SCV004826800	benign	Primary dilated cardiomyopathy	2023-12-18	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004020193	SCV004898706	uncertain significance	Cardiovascular phenotype	2021-07-21	criteria provided, single submitter	clinical testing	The c.1712G>A (p.R571H) alteration is located in exon 10 (coding exon 10) of the LMNA gene. This alteration results from a G to A substitution at nucleotide position 1712, causing the arginine (R) at amino acid position 571 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Clinical Genetics, Academic Medical Center	RCV000182349	SCV001923021	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001701632	SCV001928297	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001701632	SCV001951237	likely benign	not provided		no assertion criteria provided	clinical testing