Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002654854 | SCV003522097 | uncertain significance | Sphingolipid activator protein 1 deficiency | 2022-09-27 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 240 of the PSAP protein (p.Ile240Val). This variant is present in population databases (rs745994939, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with PSAP-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 | RCV002638456 | SCV003660912 | uncertain significance | Inborn genetic diseases | 2022-11-03 | criteria provided, single submitter | clinical testing | The c.718A>G (p.I240V) alteration is located in exon 6 (coding exon 6) of the PSAP gene. This alteration results from a A to G substitution at nucleotide position 718, causing the isoleucine (I) at amino acid position 240 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Gene |
RCV003229936 | SCV003927309 | uncertain significance | not provided | 2022-11-28 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge |