Submissions for variant NM_201384.3(PLEC):c.8801C>T (p.Thr2934Met)

gnomAD frequency: 0.00013  dbSNP: rs368122904

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000369753	SCV000333703	uncertain significance	not provided	2015-08-21	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000529817	SCV000650453	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	2023-11-24	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 2961 of the PLEC protein (p.Thr2961Met). This variant is present in population databases (rs368122904, gnomAD 0.03%). This missense change has been observed in individual(s) with arthrogryposis (PMID: 31230720). ClinVar contains an entry for this variant (Variation ID: 282308). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Fulgent Genetics, Fulgent Genetics	RCV000764749	SCV000895887	uncertain significance	Epidermolysis bullosa simplex 5B, with muscular dystrophy; Junctional epidermolysis bullosa with pyloric atresia; 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	2018-10-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000369753	SCV001765174	uncertain significance	not provided	2023-09-26	criteria provided, single submitter	clinical testing	Observed with a missense variant on the opposite allele (in trans) in a patient with distal arthrogryposis in the literature, although additional clinical information was limited (Pehlivan et al., 2019); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variant in a gene in which most reported pathogenic variants are truncating/loss of function; This variant is associated with the following publications: (PMID: 34426522, 31230720)
Revvity Omics, Revvity	RCV000369753	SCV003816678	uncertain significance	not provided	2020-10-06	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV005355588	SCV005912553	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy	2021-07-30	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV001007791	SCV001167477	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2Q		no assertion criteria provided	research