Submissions for variant NM_201384.3(PLEC):c.6874C>T (p.Arg2292Ter)

gnomAD frequency: 0.00002  dbSNP: rs387906802

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001007967	SCV001167695	pathogenic	not provided	2019-02-04	criteria provided, single submitter	clinical testing	The R2319X variant in the PLEC gene has been reported previously in the homozygous or compound heterozygous state in multiple individuals with epidermolysis bullosa (EB) with muscular dystrophy (EBS-MD) and also in one patient with EBS-MD and myasthenic syndrome (Takahashi et al., 2005; Yin et al., 2015; Vahidnezhad et al., 2017; Selcen et al., 2011). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R2319X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret R2319X as a pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001387924	SCV001588681	pathogenic	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	2022-05-20	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg2319*) in the PLEC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PLEC are known to be pathogenic (PMID: 20301336, 20447487, 21109228, 23289980, 28824526). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 30174). This premature translational stop signal has been observed in individuals with autosomal recessive epidermolysis bullosa simplex with muscular dystrophy (PMID: 15659326, 28830826). This variant is present in population databases (rs387906802, gnomAD 0.007%).
OMIM	RCV000023092	SCV000044383	pathogenic	Epidermolysis bullosa simplex 5B, with muscular dystrophy	2011-01-25	no assertion criteria provided	literature only
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001007967	SCV001743415	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001007967	SCV001952178	pathogenic	not provided		no assertion criteria provided	clinical testing
OMIM	RCV002273816	SCV002558796	pathogenic	Epidermolysis bullosa simplex with nail dystrophy	2011-01-25	no assertion criteria provided	literature only