ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.848A>G (p.Asn283Ser) (rs765241364)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000621498 SCV000737998 uncertain significance Cardiovascular phenotype 2017-05-03 criteria provided, single submitter clinical testing The p.N283S variant (also known as c.848A>G), located in coding exon 5 of the LMNA gene, results from an A to G substitution at nucleotide position 848. The asparagine at codon 283 is replaced by serine, an amino acid with highly similar properties. This variant was detected in a cohort of patients with with sporadic inclusion body myositis, and was possibly associated with Emery-Dreifuss muscular dystrophy; however, clinical details were not provided (Weihl CC et al. Neuromuscul Disord. 2015;25:289-96). This amino acid position is not well conserved in available vertebrate species, and serine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000701219 SCV000830010 uncertain significance Charcot-Marie-Tooth disease, type 2 2019-09-12 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 283 of the LMNA protein (p.Asn283Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs765241364, ExAC 0.003%). This variant has been reported in an individual affected with inclusion body myositis (PMID: 25617006). This variant is also known as N171S in the literature. 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. 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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000733487 SCV000861563 uncertain significance not provided 2018-06-01 criteria provided, single submitter clinical testing
Molecular Genetics Laboratory,London Health Sciences Centre RCV001172626 SCV001335689 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Color RCV001187553 SCV001354373 uncertain significance Cardiomyopathy 2019-04-08 criteria provided, single submitter clinical testing

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