ClinVar Miner

Submissions for variant NM_201384.3(PLEC):c.9223C>T (p.Arg3075Trp)

gnomAD frequency: 0.00006  dbSNP: rs376638828
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493669 SCV000581765 uncertain significance not provided 2017-05-01 criteria provided, single submitter clinical testing The R3102W variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R3102W variant is observed in 4/8340 (0.05%) alleles from individuals of East Asian background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This 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 that is conserved in mammals; however, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with PLEC-related disorders (Stenson et al., 2014). In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Labcorp Genetics (formerly Invitae), Labcorp RCV000550224 SCV000650466 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 2023-04-24 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. 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. ClinVar contains an entry for this variant (Variation ID: 429245). This variant has not been reported in the literature in individuals affected with PLEC-related conditions. This variant is present in population databases (rs376638828, gnomAD 0.08%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 3102 of the PLEC protein (p.Arg3102Trp).
Ambry Genetics RCV002524014 SCV003685410 uncertain significance Inborn genetic diseases 2022-02-04 criteria provided, single submitter clinical testing The c.9304C>T (p.R3102W) alteration is located in exon 33 (coding exon 32) of the PLEC gene. This alteration results from a C to T substitution at nucleotide position 9304, causing the arginine (R) at amino acid position 3102 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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