ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.1466T>G (p.Leu489Arg)

dbSNP: rs1558132909
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000727585 SCV000854831 uncertain significance not provided 2018-03-02 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001213786 SCV001385436 likely pathogenic Charcot-Marie-Tooth disease type 2 2019-11-04 criteria provided, single submitter clinical testing This sequence change replaces leucine with arginine at codon 489 of the LMNA protein (p.Leu489Arg). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of laminopathies (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 592239). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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