Submissions for variant NM_201384.3(PLEC):c.5329_5330inv (p.Glu1777Ser)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000519081	SCV000621045	uncertain significance	not specified	2017-09-18	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the PLEC gene. The c.5410_5411delGAinsTC variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.5410_5411delGAinsTC variant is not observed in large population cohorts (Lek et al., 2016). The c.5410_5411delGAinsTC variant results in an in-frame change of a single Glutamic acid residue to a Serine residue, denoted p.Glu1804Ser. The c.5410_5411delGAinsTC variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003766967	SCV004608090	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	2023-12-20	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with serine, which is neutral and polar, at codon 1804 of the PLEC protein (p.Glu1804Ser). This variant is present in population databases (no rsID available, gnomAD 0.002%). 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: 452255). 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.