ClinVar Miner

Submissions for variant NM_201384.3(PLEC):c.9658C>T (p.Arg3220Trp)

gnomAD frequency: 0.00024  dbSNP: rs200643300
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000548938 SCV000650480 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 2025-01-21 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 3247 of the PLEC protein (p.Arg3247Trp). This variant is present in population databases (rs200643300, gnomAD 0.04%). 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: 471676). 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. 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.
Eurofins Ntd Llc (ga) RCV000591559 SCV000703208 uncertain significance not provided 2017-11-13 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000591559 SCV003814946 uncertain significance not provided 2019-01-09 criteria provided, single submitter clinical testing
GeneDx RCV000591559 SCV003852973 uncertain significance not provided 2024-07-11 criteria provided, single submitter clinical testing Reported in a patient with pediatric left ventricular noncompaction (LVNC), but the variant did not segregate with disease in the family (PMID: 34752814); Missense variant in a gene in which most reported pathogenic variants are truncating/loss of function; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34752814)
Breakthrough Genomics, Breakthrough Genomics RCV000591559 SCV005196164 uncertain significance not provided criteria provided, single submitter not provided
PreventionGenetics, part of Exact Sciences RCV004737823 SCV005367130 uncertain significance PLEC-related disorder 2024-04-03 no assertion criteria provided clinical testing The PLEC c.9739C>T variant is predicted to result in the amino acid substitution p.Arg3247Trp. This variant, along with missense variants in other genes, has been reported in a pediatric patient with left ventricular noncompaction and was found to be inherited from a parent without arrhythmia (Collyer J et al. 2021. PubMed ID: 34752814). This variant is reported in 0.039% of alleles in individuals of African 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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