ClinVar Miner

Submissions for variant NM_000445.5(PLEC):c.5308G>A (p.Ala1770Thr) (rs781946435)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724944 SCV000332620 uncertain significance not provided 2015-07-23 criteria provided, single submitter clinical testing
GeneDx RCV000273380 SCV000729676 likely benign not specified 2018-01-10 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000537647 SCV000650313 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 2018-05-16 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 1770 of the PLEC protein (p.Ala1770Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. While this variant is present in population databases (rs781946435), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. 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: 281701). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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