ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.1445G>T (p.Arg482Leu) (rs11575937)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000015580 SCV000915360 uncertain significance Familial partial lipodystrophy 2 2019-01-09 criteria provided, single submitter clinical testing The LMNA c.1445G>T (p.Arg482Leu) variant has been identified in one family with partial lipodystrophy (Shackleton et al. 2000). This variant was found in a heterozygous state in the proband, affected mother, and affected maternal uncle and was not found in the sibling (age 10 years, whose disease state was equivocal at the time of ascertainment), unaffected father, or unaffected maternal grandmother. The p.Arg482Leu variant was absent from 100 control chromosomes and is not found in the 1000 Genomes Project, the Exome Sequencing Project, the Exome Aggregation Consortium, or the Genome Aggregation Database. The Arg482 residue is highly conserved and is a known variant hotspot. Functional studies showed that the p.Arg482Leu variant resulted in the formation of abnormal nuclear aggregates of lamin and failure of lamin to interact with emerin (Capanni et al. 2003; Hubner et al. 2006). Meaburn et al. (2007) showed that the variant resulted in a significant increase in percentage of cells undergoing apoptosis and in the repositioning of chromosomes 13 and X away from the nuclear periphery. Perepelina et al. (2018) demonstrated decreased Notch signaling for the p.Arg482Leu variant compared to controls and decreased adipogenic differentiation in response to Notch activation. Based on the collective evidence, the p.Arg482Leu variant is classified as a variant of unknown significance but suspicious for pathogenicity for familial partial lipodystrophy. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Illumina Clinical Services Laboratory,Illumina RCV001097055 SCV001253306 uncertain significance Mandibuloacral dysplasia with type A lipodystrophy 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001097056 SCV001253307 uncertain significance Emery-Dreifuss muscular dystrophy 2, autosomal dominant 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001098782 SCV001255170 uncertain significance Dilated cardiomyopathy 1A 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001098783 SCV001255171 uncertain significance Lipoatrophy with Diabetes, Hepatic Steatosis, Hypertrophic Cardiomyopathy, and Leukomelanodermic Papules 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001098784 SCV001255172 uncertain significance Hutchinson-Gilford syndrome 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001098785 SCV001255173 uncertain significance Charcot-Marie-Tooth disease type 2B1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001098786 SCV001255174 uncertain significance Emery-Dreifuss muscular dystrophy 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001098787 SCV001255175 uncertain significance Lethal tight skin contracture syndrome 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001098788 SCV001255176 uncertain significance Congenital muscular dystrophy, LMNA-related 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
OMIM RCV000015580 SCV000035845 pathogenic Familial partial lipodystrophy 2 2000-02-01 no assertion criteria provided literature only
Epithelial Biology; Institute of Medical Biology, Singapore RCV000057300 SCV000088413 not provided not provided no assertion provided not provided

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