Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000214054 | SCV000279792 | likely pathogenic | not provided | 2016-01-22 | criteria provided, single submitter | clinical testing | The c.2003_2015del13 variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The c.2003_2015del13 variant causes a frameshift starting with codon Leucine 668, changes this amino acid to a Proline residue and creates a premature Stop codon at position 14 of the new reading frame, denoted p.Leu668ProfsX14. This variant is predicted to cause loss of normal protein function through protein truncation as the last 56 amino acids of the LRSAM1 protein are lost and replaced with 13 incorrect amino acids. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |
| Labcorp Genetics |
RCV000696532 | SCV000825096 | likely pathogenic | Charcot-Marie-Tooth disease axonal type 2P | 2022-09-09 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the C-terminus of the LRSAM1 protein. Other variant(s) that disrupt this region (p.Glu674Valfs*11, p.Glu682Glyfs*5, c.2047-1G>A) have been observed in individuals with LRSAM1-related conditions (PMID: 22781092, 28286897, 29341362; Invitae). This suggests that this may be a clinically significant region of the protein. ClinVar contains an entry for this variant (Variation ID: 234769). This premature translational stop signal has been observed in individual(s) with LRSAM1-related conditions (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu668Profs*14) in the LRSAM1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 56 amino acid(s) of the LRSAM1 protein. |
| MGZ Medical Genetics Center | RCV000696532 | SCV002578918 | likely pathogenic | Charcot-Marie-Tooth disease axonal type 2P | 2022-03-17 | criteria provided, single submitter | clinical testing |