Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001566516 | SCV001790048 | uncertain significance | not provided | 2020-07-14 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function |
Invitae | RCV001566516 | SCV002188609 | uncertain significance | not provided | 2021-09-08 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with serine at codon 443 of the TPP1 protein (p.Asn443Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs139343938, ExAC 0.03%). This variant has not been reported in the literature in individuals affected with TPP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 457938). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 | RCV002527680 | SCV003742009 | uncertain significance | Inborn genetic diseases | 2022-12-06 | criteria provided, single submitter | clinical testing | The c.1328A>G (p.N443S) alteration is located in exon 11 (coding exon 11) of the TPP1 gene. This alteration results from a A to G substitution at nucleotide position 1328, causing the asparagine (N) at amino acid position 443 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Natera, |
RCV001834751 | SCV002094814 | uncertain significance | Neuronal ceroid lipofuscinosis 2 | 2019-11-11 | no assertion criteria provided | clinical testing |