ClinVar Miner

Submissions for variant NM_201384.3(PLEC):c.12572A>G (p.Lys4191Arg)

gnomAD frequency: 0.00009  dbSNP: rs782075595
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002024112 SCV002315131 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 2023-02-27 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 4218 of the PLEC protein (p.Lys4218Arg). This variant is present in population databases (rs782075595, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with PLEC-related conditions. ClinVar contains an entry for this variant (Variation ID: 1518770). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PLEC protein function. 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.
Revvity Omics, Revvity RCV003130682 SCV003817226 uncertain significance not provided 2022-12-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV003289400 SCV004007734 uncertain significance Inborn genetic diseases 2023-03-20 criteria provided, single submitter clinical testing The c.12653A>G (p.K4218R) alteration is located in exon 33 (coding exon 32) of the PLEC gene. This alteration results from a A to G substitution at nucleotide position 12653, causing the lysine (K) at amino acid position 4218 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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