ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.1306A>G (p.Thr436Ala) (rs876657849)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000824027 SCV000964902 uncertain significance Charcot-Marie-Tooth disease, type 2 2018-08-30 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 436 of the LMNA protein (p.Thr436Ala). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with LMNA-related disease. ClinVar contains an entry for this variant (Variation ID: 228802). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55"). 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.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000218886 SCV000271922 uncertain significance not specified 2015-06-24 criteria provided, single submitter clinical testing The p.Thr436Ala variant in LMNA has not been previously reported in individuals with cardiomyopathy or in large population studies. Computational prediction to ols and conservation analysis do not provide strong support for or against an im pact to the protein. In summary, the clinical significance of the p.Thr436Ala va riant is uncertain.

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