Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV001822574 | SCV002065385 | uncertain significance | not specified | 2021-06-25 | criteria provided, single submitter | clinical testing | DNA sequence analysis of the LYZ gene demonstrated a sequence change, c.209C>G, in exon 2 that results in an amino acid change, p.Thr70Ser. This sequence change is absent from known population databases (gnomAD). The p.Thr70Ser change affects a highly conserved amino acid residue located in a domain of the LYZ protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Thr70Ser substitution. This sequence change does not appear to have been previously described in patients with LYZ-related disorders. Due to the lack of sufficient evidences, the clinical significance of the p.Thr70Ser change remains unknown at this time. |
Fulgent Genetics, |
RCV002503324 | SCV002814635 | uncertain significance | Familial visceral amyloidosis, Ostertag type | 2022-03-30 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV003728035 | SCV004523796 | uncertain significance | not provided | 2023-01-14 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 1337976). This variant has not been reported in the literature in individuals affected with LYZ-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 70 of the LYZ protein (p.Thr70Ser). 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. |