Submissions for variant NM_201384.3(PLEC):c.6343G>A (p.Glu2115Lys)

gnomAD frequency: 0.00004  dbSNP: rs782713908

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000543341	SCV000650374	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	2024-11-27	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 2142 of the PLEC protein (p.Glu2142Lys). This variant is present in population databases (rs782713908, gnomAD 0.2%), including at least one homozygous and/or hemizygous individual. 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: 471629). 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 tolerated. 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)	RCV000727828	SCV000855255	uncertain significance	not provided	2017-11-16	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001335327	SCV001528456	uncertain significance	Epidermolysis bullosa simplex 5B, with muscular dystrophy	2018-10-24	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Revvity Omics, Revvity	RCV000727828	SCV003817336	uncertain significance	not provided	2021-10-13	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004955649	SCV005471546	uncertain significance	Inborn genetic diseases	2024-10-29	criteria provided, single submitter	clinical testing	The c.6424G>A (p.E2142K) 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 6424, causing the glutamic acid (E) at amino acid position 2142 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV004543192	SCV004781707	likely benign	PLEC-related disorder	2024-06-10	no assertion criteria provided	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).