Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000814080 | SCV000954477 | uncertain significance | Muscular dystrophy-dystroglycanopathy type B6 | 2022-10-25 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 631 of the LARGE1 protein (p.Thr631Met). This variant is present in population databases (rs368043810, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with LARGE1-related conditions. ClinVar contains an entry for this variant (Variation ID: 657473). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt LARGE1 protein function. 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. |
Gene |
RCV001786418 | SCV002028868 | likely benign | not provided | 2021-04-15 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV002539943 | SCV003677201 | uncertain significance | Inborn genetic diseases | 2022-07-08 | criteria provided, single submitter | clinical testing | The c.1892C>T (p.T631M) alteration is located in exon 15 (coding exon 13) of the LARGE1 gene. This alteration results from a C to T substitution at nucleotide position 1892, causing the threonine (T) at amino acid position 631 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Revvity Omics, |
RCV001786418 | SCV003816471 | uncertain significance | not provided | 2021-02-04 | criteria provided, single submitter | clinical testing |