ClinVar Miner

Submissions for variant NM_201384.3(PLEC):c.10532G>A (p.Gly3511Asp)

gnomAD frequency: 0.00004  dbSNP: rs200972761
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000727854 SCV000620290 uncertain significance not provided 2021-06-21 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variant in a gene in which most reported pathogenic variants are truncating/loss-of-function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533)
Eurofins Ntd Llc (ga) RCV000727854 SCV000855320 uncertain significance not provided 2017-08-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001067129 SCV001232167 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 2023-09-21 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. 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 not expected to disrupt PLEC protein function. ClinVar contains an entry for this variant (Variation ID: 451570). This variant has not been reported in the literature in individuals affected with PLEC-related conditions. This variant is present in population databases (rs200972761, gnomAD 0.008%). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 3538 of the PLEC protein (p.Gly3538Asp).
Ambry Genetics RCV002525206 SCV003729956 uncertain significance Inborn genetic diseases 2022-12-01 criteria provided, single submitter clinical testing The c.10613G>A (p.G3538D) alteration is located in exon 33 (coding exon 32) of the PLEC gene. This alteration results from a G to A substitution at nucleotide position 10613, causing the glycine (G) at amino acid position 3538 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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