Submissions for variant NM_170707.4(LMNA):c.1961G>A (p.Arg654Gln)

gnomAD frequency: 0.00001  dbSNP: rs768986279

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Molecular Genetics Laboratory, London Health Sciences Centre	RCV001172623	SCV001335686	uncertain significance	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001183493	SCV001349239	uncertain significance	Cardiomyopathy	2020-01-14	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with glutamine at codon 654 of the lamin A protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. 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 3/246770 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Invitae	RCV001298870	SCV001487941	uncertain significance	Charcot-Marie-Tooth disease type 2	2022-07-11	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 654 of the LMNA protein (p.Arg654Gln). This variant is present in population databases (rs768986279, gnomAD 0.006%). 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: 916766). 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: "Possibly 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.
Revvity Omics, Revvity	RCV003130171	SCV003814696	uncertain significance	not provided	2020-09-24	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV004000280	SCV004827491	uncertain significance	Primary dilated cardiomyopathy	2023-05-31	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with glutamine at codon 654 of the lamin A protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. 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 3/246770 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.