Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001323707 | SCV001514634 | 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 | 2020-03-26 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with PLEC-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with alanine at codon 4360 of the PLEC protein (p.Thr4360Ala). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and alanine. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |
Ambry Genetics | RCV004656524 | SCV005150107 | uncertain significance | Inborn genetic diseases | 2024-03-30 | criteria provided, single submitter | clinical testing | The c.13078A>G (p.T4360A) alteration is located in exon 33 (coding exon 32) of the PLEC gene. This alteration results from a A to G substitution at nucleotide position 13078, causing the threonine (T) at amino acid position 4360 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |