Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001389709 | SCV001591160 | pathogenic | not provided | 2021-01-01 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Asp2913Metfs*2) in the LAMA1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs776769192, ExAC 0.001%). This variant has not been reported in the literature in individuals with LAMA1-related conditions. Loss-of-function variants in LAMA1 are known to be pathogenic (PMID: 25105227, 26932191). |
| Pittsburgh Clinical Genomics Laboratory, |
RCV004783967 | SCV005397628 | likely pathogenic | Ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome | 2023-12-08 | criteria provided, single submitter | clinical testing | This sequence variant is a single nucleotide deletion (delC) in exon 61 of 63 of LAMA1 which results in an early termination codon 2 amino acids downstream of the frameshift at amino acid 2913. This variant is predicted to generate a non-functional allele through either the expression of a truncated protein or a loss of laminin subunit alpha 1 expression due to nonsense mediated decay. This is a previously reported variant (ClinVar 1075978) that has not been observed in individuals affected by LAMA1-related disorders in the published literature, to our knowledge. This variant is present in 1 of 251420 alleles (0.0004%) in the gnomAD population dataset. Studies examining the functional consequence of this variant have not been published, to our knowledge. Based upon the evidence, we consider this variant to be likely pathogenic. ACMG Criteria: PM2, PVS1 |