Submissions for variant NM_201384.3(PLEC):c.4351G>A (p.Glu1451Lys)

gnomAD frequency: 0.00073  dbSNP: rs868906137

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000725142	SCV000334418	uncertain significance	not provided	2017-02-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000725142	SCV000577413	likely benign	not provided	2020-03-27	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000534113	SCV000650276	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	2023-12-07	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 1478 of the PLEC protein (p.Glu1478Lys). This variant is present in population databases (no rsID available, gnomAD 0.1%), including at least one homozygous and/or hemizygous individual. This missense change has been observed in individual(s) with clinical features of limb-girdle muscular dystrophy (Invitae). ClinVar contains an entry for this variant (Variation ID: 282780). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
CeGaT Center for Human Genetics Tuebingen	RCV000725142	SCV001248535	likely benign	not provided	2023-01-01	criteria provided, single submitter	clinical testing	PLEC: BS2
MGZ Medical Genetics Center	RCV002288959	SCV002580793	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2Q	2022-03-14	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000725142	SCV003817343	uncertain significance	not provided	2023-09-06	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004737404	SCV005350443	uncertain significance	PLEC-related disorder	2024-07-22	no assertion criteria provided	clinical testing	The PLEC c.4432G>A variant is predicted to result in the amino acid substitution p.Glu1478Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.11% of alleles in individuals of Latino descent in gnomAD, which is likely too common for an undocumented disease-causing variant. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.