Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001046249 | SCV001210144 | uncertain significance | Familial aplasia of the vermis | 2022-11-08 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 226 of the INPP5E protein (p.Leu226Phe). This variant is present in population databases (rs761485683, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with INPP5E-related conditions. ClinVar contains an entry for this variant (Variation ID: 843588). 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 tolerated. 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 | RCV004986758 | SCV005606084 | uncertain significance | Inborn genetic diseases | 2024-10-12 | criteria provided, single submitter | clinical testing | The c.676C>T (p.L226F) alteration is located in exon 1 (coding exon 1) of the INPP5E gene. This alteration results from a C to T substitution at nucleotide position 676, causing the leucine (L) at amino acid position 226 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |