Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001971646 | SCV002261343 | uncertain significance | Hereditary spastic paraplegia 50 | 2021-08-26 | criteria provided, single submitter | clinical testing | 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. 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. This variant has not been reported in the literature in individuals with AP4M1-related conditions. This variant is present in population databases (rs781616312, ExAC 0.009%). This sequence change replaces arginine with cysteine at codon 271 of the AP4M1 protein (p.Arg271Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. |
Ambry Genetics | RCV004956046 | SCV005454551 | uncertain significance | Inborn genetic diseases | 2024-08-10 | criteria provided, single submitter | clinical testing | The c.811C>T (p.R271C) alteration is located in exon 10 (coding exon 10) of the AP4M1 gene. This alteration results from a C to T substitution at nucleotide position 811, causing the arginine (R) at amino acid position 271 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |