Submissions for variant NM_201384.3(PLEC):c.13636G>A (p.Val4546Met)

gnomAD frequency: 0.00010  dbSNP: rs573424409

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000422312	SCV000533266	likely benign	not specified	2017-07-28	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Athena Diagnostics	RCV000422312	SCV000614607	uncertain significance	not specified	2016-09-26	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000725526	SCV000701000	uncertain significance	not provided	2017-01-25	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000705982	SCV000835008	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	2024-09-03	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 4573 of the PLEC protein (p.Val4573Met). This variant is present in population databases (rs573424409, 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: 390440). 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.
Revvity Omics, Revvity	RCV000725526	SCV003815525	uncertain significance	not provided	2020-08-11	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004022470	SCV005006546	uncertain significance	Inborn genetic diseases	2023-11-13	criteria provided, single submitter	clinical testing	The c.13717G>A (p.V4573M) 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 13717, causing the valine (V) at amino acid position 4573 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.