Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001321808 | SCV001512655 | 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 | 2024-01-04 | 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 839 of the PLEC protein (p.Val839Met). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with PLEC-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 1021959). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae 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. |
Revvity Omics, |
RCV003132410 | SCV003808522 | uncertain significance | not provided | 2019-02-22 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004035042 | SCV005006556 | uncertain significance | Inborn genetic diseases | 2023-10-06 | criteria provided, single submitter | clinical testing | The c.2515G>A (p.V839M) alteration is located in exon 21 (coding exon 20) of the PLEC gene. This alteration results from a G to A substitution at nucleotide position 2515, causing the valine (V) at amino acid position 839 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |