ClinVar Miner

Submissions for variant NM_000445.5(PLEC):c.5602G>A (p.Ala1868Thr) (rs201657125)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000358773 SCV000333946 uncertain significance not provided 2015-10-13 criteria provided, single submitter clinical testing
Invitae RCV000560655 SCV000650332 uncertain significance Epidermolysa bullosa simplex and limb girdle muscular dystrophy; Epidermolysis bullosa simplex, Ogna type; Epidermolysis bullosa simplex with pyloric atresia; Limb-girdle muscular dystrophy, type 2Q; Epidermolysis bullosa simplex with nail dystrophy 2018-12-06 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 1868 of the PLEC protein (p.Ala1868Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs201657125, ExAC 0.2%). This variant has not been reported in the literature in individuals with a PLEC-related disease. ClinVar contains an entry for this variant (Variation ID: 282455). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Unknown"; Align-GVGD: "Class C55". The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, this variant has uncertain impact on PLEC function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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