Submissions for variant NM_201384.3(PLEC):c.6536G>A (p.Arg2179Gln)

gnomAD frequency: 0.00064  dbSNP: rs117962829

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000724990	SCV000333020	uncertain significance	not provided	2015-07-15	criteria provided, single submitter	clinical testing
Invitae	RCV000554395	SCV000650383	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	2024-01-28	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 2206 of the PLEC protein (p.Arg2206Gln). This variant is present in population databases (rs117962829, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with clinical features of PLEC-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 196752). 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.
GeneDx	RCV000724990	SCV000714326	likely benign	not provided	2021-02-27	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002517719	SCV003680603	uncertain significance	Inborn genetic diseases	2022-05-18	criteria provided, single submitter	clinical testing	The c.6617G>A (p.R2206Q) alteration is located in exon 32 (coding exon 31) of the PLEC gene. This alteration results from a G to A substitution at nucleotide position 6617, causing the arginine (R) at amino acid position 2206 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV003907604	SCV004724529	likely benign	PLEC-related condition	2023-08-16	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).