Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV000987769 | SCV001137218 | likely pathogenic | Merosin deficient congenital muscular dystrophy | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001858676 | SCV002141401 | uncertain significance | LAMA2-related muscular dystrophy | 2024-03-11 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 1079 of the LAMA2 protein (p.Cys1079Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of LAMA2-related conditions (PMID: 32528171). ClinVar contains an entry for this variant (Variation ID: 802261). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on LAMA2 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001858676 | SCV005422243 | likely pathogenic | LAMA2-related muscular dystrophy | 2024-10-22 | criteria provided, single submitter | clinical testing | Variant summary: LAMA2 c.3235T>C (p.Cys1079Arg) results in a non-conservative amino acid change located in the Laminin-type EGF domain (IPR002049) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251404 control chromosomes. c.3235T>C has been reported in the literature in individuals affected with and/or with clinical features of Laminin Alpha 2-Related Dystrophy (e.g. Topf_2020, Camelo_2024) . These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 38747280, 37182895, 32528171). ClinVar contains an entry for this variant (Variation ID: 802261). Based on the evidence outlined above, the variant was classified as likely pathogenic. |