Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001053445 | SCV001217705 | uncertain significance | Dilated cardiomyopathy 1JJ | 2022-04-12 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 211 of the LAMA4 protein (p.Asn211His). This variant is present in population databases (rs371848733, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with clinical features of dilated cardiomyopathy (PMID: 28416588). ClinVar contains an entry for this variant (Variation ID: 180389). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |
| Ambry Genetics | RCV002362838 | SCV002660606 | uncertain significance | Cardiovascular phenotype | 2022-09-13 | criteria provided, single submitter | clinical testing | The p.N211H variant (also known as c.631A>C), located in coding exon 5 of the LAMA4 gene, results from an A to C substitution at nucleotide position 631. The asparagine at codon 211 is replaced by histidine, an amino acid with similar properties. This variant was reported in a dilated cardiomyopathy (DCM) cohort; however, clinical details were limited (Dal Ferro M et al. Heart, 2017 11;103:1704-1710). This amino acid position is well conserved in available vertebrate species; however, histidine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Blueprint Genetics | RCV000157275 | SCV000207006 | uncertain significance | Primary dilated cardiomyopathy | 2014-09-29 | no assertion criteria provided | clinical testing |