Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000823484 | SCV000964345 | uncertain significance | Brody myopathy | 2018-11-07 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with isoleucine at codon 805 of the ATP2A1 protein (p.Thr805Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs778571371, ExAC 0.006%). This variant has not been reported in the literature in individuals with ATP2A1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but 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 | RCV002535987 | SCV003646860 | uncertain significance | Inborn genetic diseases | 2022-10-12 | criteria provided, single submitter | clinical testing | The c.2414C>T (p.T805I) alteration is located in exon 17 (coding exon 17) of the ATP2A1 gene. This alteration results from a C to T substitution at nucleotide position 2414, causing the threonine (T) at amino acid position 805 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |