ClinVar Miner

Submissions for variant NM_201384.3(PLEC):c.9823C>T (p.Arg3275Cys)

gnomAD frequency: 0.00002  dbSNP: rs782733657
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000487352 SCV000572740 uncertain significance not provided 2017-09-11 criteria provided, single submitter clinical testing The R3302C variant in the PLEC gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R3302C variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R3302C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where amino acids with similar properties to Arginine are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R3302C as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000648489 SCV000770309 uncertain significance Epidermolysis bullosa simplex 5B, with muscular dystrophy; Epidermolysis bullosa simplex, Ogna type; Epidermolysis bullosa simplex 5C, with pyloric atresia; Autosomal recessive limb-girdle muscular dystrophy type 2Q; Epidermolysis bullosa simplex with nail dystrophy 2023-04-16 criteria provided, single submitter clinical testing 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. ClinVar contains an entry for this variant (Variation ID: 423095). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 3302 of the PLEC protein (p.Arg3302Cys). This variant is present in population databases (rs782733657, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with PLEC-related conditions.
Athena Diagnostics RCV000487352 SCV001475975 uncertain significance not provided 2020-06-05 criteria provided, single submitter clinical testing

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