ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.1390A>G (p.Met464Val)

gnomAD frequency: 0.00009  dbSNP: rs200262654
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000725643 SCV000590650 uncertain significance not provided 2020-04-13 criteria provided, single submitter clinical testing Has not been previously published in association with LMNA-related disorders; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 432879; Landrum et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 30564623, 28663758)
Eurofins Ntd Llc (ga) RCV000725643 SCV000701060 uncertain significance not provided 2017-05-24 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000772026 SCV000904982 uncertain significance Cardiomyopathy 2023-06-08 criteria provided, single submitter clinical testing This missense variant replaces methionine with valine at codon 464 of the LMNA protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with cardiomyopathy and conduction defect (PMID: 31383942). This variant has been identified in 7/282082 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 RCV000800973 SCV000940720 likely benign Charcot-Marie-Tooth disease type 2 2023-11-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV002395208 SCV002695985 uncertain significance Cardiovascular phenotype 2021-05-28 criteria provided, single submitter clinical testing The p.M464V variant (also known as c.1390A>G), located in coding exon 8 of the LMNA gene, results from an A to G substitution at nucleotide position 1390. The methionine at codon 464 is replaced by valine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002506209 SCV002816620 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 2021-11-04 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000725643 SCV004236251 uncertain significance not provided 2023-06-27 criteria provided, single submitter clinical testing

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