ClinVar Miner

Submissions for variant NM_201384.3(PLEC):c.12476G>A (p.Arg4159His)

gnomAD frequency: 0.00001  dbSNP: rs200506691
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000592063 SCV000704275 uncertain significance not provided 2016-12-27 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001070449 SCV001235680 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 2023-10-24 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 4186 of the PLEC protein (p.Arg4186His). This variant is present in population databases (rs200506691, gnomAD 0.006%). 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: 498993). 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 with a negative predictive value of 80%. 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 RCV000592063 SCV003816690 uncertain significance not provided 2021-12-21 criteria provided, single submitter clinical testing
Ambry Genetics RCV004955685 SCV005476094 uncertain significance Inborn genetic diseases 2024-11-25 criteria provided, single submitter clinical testing The c.12557G>A (p.R4186H) 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 12557, causing the arginine (R) at amino acid position 4186 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV004737863 SCV005353915 uncertain significance PLEC-related disorder 2024-04-03 no assertion criteria provided clinical testing The PLEC c.12557G>A variant is predicted to result in the amino acid substitution p.Arg4186His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0058% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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