ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.1517A>C (p.His506Pro) (rs878855233)

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000227241 SCV000291550 uncertain significance Charcot-Marie-Tooth disease, type 2 2019-12-23 criteria provided, single submitter clinical testing This sequence change replaces histidine with proline at codon 506 of the LMNA protein (p.His506Pro). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with dilated cardiomyopathy (DCM) (PMID: 27813223). ClinVar contains an entry for this variant (Variation ID: 242003). Experimental studies have shown that this variant impacts the interaction between prelamin A and Ankrd2, and leads to altered Ankrd2 cellular localization (PMID: 28531892). 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.
GeneDx RCV000235371 SCV000292723 uncertain significance not provided 2015-06-04 criteria provided, single submitter clinical testing The H506P variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The H506P variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The H506P variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in most mammals, however Proline is the wild type residue at this position in platypus and Alanine is present at this position in alpaca. Missense mutations in this residue (H506D) and nearby residues (W498R, W498C, L512P) have been reported in the Human Gene Mutation Database in association with metabolic laminopathy, muscular dystrophy and myopathy (Stenson et al., 2014), supporting the functional importance of this region of the protein. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Center for Human Genetics,University of Leuven RCV000498163 SCV000579568 uncertain significance Hypertrophic cardiomyopathy 2017-04-30 criteria provided, single submitter clinical testing
Color RCV000777786 SCV000913764 uncertain significance Cardiomyopathy 2019-04-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001098894 SCV001255291 uncertain significance Lipoatrophy with Diabetes, Hepatic Steatosis, Hypertrophic Cardiomyopathy, and Leukomelanodermic Papules 2019-06-06 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 RCV001098895 SCV001255292 uncertain significance Emery-Dreifuss muscular dystrophy 2, autosomal dominant 2019-06-06 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 RCV001098896 SCV001255293 uncertain significance Dilated cardiomyopathy 1A 2019-06-06 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 RCV001100712 SCV001257243 uncertain significance Mandibuloacral dysplasia with type A lipodystrophy 2019-06-06 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 RCV001100713 SCV001257245 uncertain significance Hutchinson-Gilford syndrome 2019-06-06 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 RCV001100714 SCV001257246 uncertain significance Charcot-Marie-Tooth disease type 2B1 2019-06-06 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 RCV001100715 SCV001257247 uncertain significance Lethal tight skin contracture syndrome 2019-06-06 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 RCV001100716 SCV001257248 uncertain significance Congenital muscular dystrophy, LMNA-related 2019-06-06 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 RCV001100717 SCV001257249 uncertain significance Emery-Dreifuss muscular dystrophy 2019-06-06 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 RCV001100718 SCV001257250 uncertain significance Familial partial lipodystrophy 2 2019-06-06 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.

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