ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.860C>T (p.Ala287Val)

dbSNP: rs397517910
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000041373 SCV000065066 uncertain significance not specified 2012-02-13 criteria provided, single submitter clinical testing The Ala287Val variant (LMNA) has not been reported in the literature nor previou sly identified by our laboratory. Computational analyses (biochemical amino acid properties, conservation, PolyPhen2, SIFT, AlignGVGD) do not provide strong sup port for or against pathogenicity. In the absence of additional information, th e clinical significance of this variant cannot be determined.
Color Diagnostics, LLC DBA Color Health RCV001181114 SCV001346200 uncertain significance Cardiomyopathy 2019-11-08 criteria provided, single submitter clinical testing This missense variant replaces alanine with valine at codon 287 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/251034 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 RCV001852842 SCV002169863 uncertain significance Charcot-Marie-Tooth disease type 2 2021-04-11 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with LMNA-related conditions. ClinVar contains an entry for this variant (Variation ID: 48087). This sequence change replaces alanine with valine at codon 287 of the LMNA protein (p.Ala287Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine.

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