Submissions for variant NM_170707.4(LMNA):c.610C>G (p.Leu204Val)

dbSNP: rs1553265177

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000618027	SCV000737956	uncertain significance	Cardiovascular phenotype	2017-03-20	criteria provided, single submitter	clinical testing	The p.L204V variant (also known as c.610C>G), located in coding exon 3 of the LMNA gene, results from a C to G substitution at nucleotide position 610. The leucine at codon 204 is replaced by valine, an amino acid with highly similar properties, and is located in the coil 1b domain. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001067181	SCV001232226	uncertain significance	Charcot-Marie-Tooth disease type 2	2024-01-29	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 204 of the LMNA protein (p.Leu204Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of LMNA-related disease (PMID: 27884249; Invitae). ClinVar contains an entry for this variant (Variation ID: 519420). 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 with a positive predictive value of 95%. 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.
Color Diagnostics, LLC DBA Color Health	RCV001185566	SCV001351815	uncertain significance	Cardiomyopathy	2019-07-25	criteria provided, single submitter	clinical testing	This missense variant replaces leucine with valine at codon 204 of the LMNA protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). 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.
AiLife Diagnostics, AiLife Diagnostics	RCV002223883	SCV002501924	uncertain significance	not provided	2021-08-19	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002483720	SCV002789948	uncertain significance	Dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome; Dilated cardiomyopathy 1A; Charcot-Marie-Tooth disease type 2B1; Emery-Dreifuss muscular dystrophy 2, autosomal dominant; Heart-hand syndrome, Slovenian type; Hutchinson-Gilford syndrome; Familial partial lipodystrophy, Dunnigan type; Mandibuloacral dysplasia with type A lipodystrophy; Congenital muscular dystrophy due to LMNA mutation; Emery-Dreifuss muscular dystrophy 3, autosomal recessive; Restrictive dermopathy 2	2022-05-27	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001185566	SCV003838483	uncertain significance	Cardiomyopathy	2021-08-09	criteria provided, single submitter	clinical testing