Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000710157 | SCV000113078 | uncertain significance | not provided | 2013-04-30 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000192984 | SCV000196856 | uncertain significance | not specified | 2017-08-17 | criteria provided, single submitter | clinical testing | The V474I variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The V474I variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. This substitution occurs at a position that is conserved across species within the predicted lumenal domain of the LARGE protein. However, the V474I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in LARGE panel. |
Genetic Services Laboratory, |
RCV000192984 | SCV000247832 | uncertain significance | not specified | 2015-07-07 | criteria provided, single submitter | clinical testing | |
Athena Diagnostics | RCV000710157 | SCV000613992 | uncertain significance | not provided | 2018-04-13 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000540677 | SCV000638975 | uncertain significance | Muscular dystrophy-dystroglycanopathy type B6 | 2024-01-22 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 474 of the LARGE1 protein (p.Val474Ile). This variant is present in population databases (rs150861748, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. 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: 95164). 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 with a negative predictive value of 80%. 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. |
Fulgent Genetics, |
RCV000764383 | SCV000895436 | uncertain significance | Muscular dystrophy-dystroglycanopathy type B6; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A6 | 2022-04-29 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV001148299 | SCV001309187 | uncertain significance | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A6 | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Illumina Laboratory Services, |
RCV000540677 | SCV001309188 | uncertain significance | Muscular dystrophy-dystroglycanopathy type B6 | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Mayo Clinic Laboratories, |
RCV000710157 | SCV001715617 | uncertain significance | not provided | 2022-12-06 | criteria provided, single submitter | clinical testing | BP4 |
ARUP Laboratories, |
RCV000710157 | SCV002048773 | uncertain significance | not provided | 2021-02-05 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003925066 | SCV004738537 | likely benign | LARGE1-related disorder | 2023-06-26 | no assertion criteria provided | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |