ClinVar Miner

Submissions for variant NM_138361.5(LRSAM1):c.497C>T (p.Pro166Leu) (rs142085060)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000459320 SCV000547850 uncertain significance Charcot-Marie-Tooth disease type 2P 2019-07-11 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 166 of the LRSAM1 protein (p.Pro166Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs142085060, ExAC 0.01%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in an individual affected with Charcot-Marie-Tooth disease type 2 (CMT2) (PMID: 26392352 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 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.

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