Total submissions: 12
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Clinical Services Laboratory, |
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, |
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, |
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, |
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, |
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, |
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, |
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, |
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, |
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, |
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, |
RCV000057300 | SCV000088413 | not provided | not provided | no assertion provided | not provided |