ClinVar Miner

Submissions for variant NM_201384.3(PLEC):c.12146C>T (p.Thr4049Met)

gnomAD frequency: 0.00001  dbSNP: rs1277411906
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Genetics, Royal Melbourne Hospital RCV002225150 SCV002503623 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2Q 2020-11-20 criteria provided, single submitter clinical testing This sequence change is predicted to replace threonine with methionine at codon 4076 of the PLEC protein (p.Thr4076Met). The threonine residue is evolutionary invariant (100 vertebrates, UCSC), and located in the plectin 25 repeat in the globular 2 region. There is a moderate physicochemical difference between threonine and methionine. The variant is absent in a large population cohort (PM2; gnomAD v2.1), and has not been reported in relevant medical literature or databases. Multiple lines of computational evidence predict a deleterious effect for the missense substitution (PP3; 6/6 algorithms). Based on the classification scheme RMH ACMG Guidelines v1.2.1, this variant is classified as VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: PM2, PP3.
Ambry Genetics RCV004047227 SCV005006526 uncertain significance Inborn genetic diseases 2024-01-08 criteria provided, single submitter clinical testing The c.12227C>T (p.T4076M) alteration is located in exon 33 (coding exon 32) of the PLEC gene. This alteration results from a C to T substitution at nucleotide position 12227, causing the threonine (T) at amino acid position 4076 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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