Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000218805 | SCV000270333 | likely benign | not specified | 2015-01-30 | criteria provided, single submitter | clinical testing | p.Pro131Leu in exon 4 of LAMA4: This variant is not expected to have clinical si gnificance due to a lack of conservation across species, including mammals. Of n ote, several mammals (rhesus, macaque, baboon and pacific walrus) have a leucine (Leu) at this position despite high nearby amino acid conservation. In addition , computational prediction tools do not suggest a high likelihood of impact to t he protein. This variant has also been identified in 5/11554 Latino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs374273620). |
| Ambry Genetics | RCV002372218 | SCV002624933 | likely benign | Cardiovascular phenotype | 2021-07-12 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Invitae | RCV002517471 | SCV002977796 | uncertain significance | Dilated cardiomyopathy 1JJ | 2022-02-22 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 227480). This variant has not been reported in the literature in individuals affected with LAMA4-related conditions. This variant is present in population databases (rs374273620, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 131 of the LAMA4 protein (p.Pro131Leu). |