Submissions for variant NM_201384.3(PLEC):c.12907G>A (p.Val4303Met)

gnomAD frequency: 0.00027  dbSNP: rs200668859

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000526531	SCV000660352	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	2025-01-31	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 4330 of the PLEC protein (p.Val4330Met). This variant is present in population databases (rs200668859, gnomAD 0.2%). 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: 478589). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt PLEC protein function with a negative predictive value of 80%. 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	RCV000999082	SCV001155498	uncertain significance	not provided	2016-06-01	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000999082	SCV002540972	uncertain significance	not provided	2021-07-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002527965	SCV003606870	uncertain significance	Inborn genetic diseases	2022-11-18	criteria provided, single submitter	clinical testing	The c.12988G>A (p.V4330M) alteration is located in exon 33 (coding exon 32) of the PLEC gene. This alteration results from a G to A substitution at nucleotide position 12988, causing the valine (V) at amino acid position 4330 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity	RCV000999082	SCV003811136	uncertain significance	not provided	2022-09-20	criteria provided, single submitter	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000999082	SCV001799701	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000999082	SCV001975020	uncertain significance	not provided		no assertion criteria provided	clinical testing