Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000150905 | SCV000198505 | likely benign | not specified | 2014-01-31 | criteria provided, single submitter | clinical testing | His138Tyr in exon 4 of LAMA4: This variant is not expected to have clinical sign ificance due to a lack of conservation across species, including mammals. Of not e, multiple mammals have a tyrosine (Tyr) at this position despite high nearby a mino acid conservation. In addition, computational analyses (AlignGVGD, PolyPhen 2, SIFT) do not suggest a high likelihood of impact to the protein. |
Invitae | RCV001244791 | SCV001418035 | uncertain significance | Dilated cardiomyopathy 1JJ | 2022-03-20 | 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 tyrosine 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: 163796). This variant has not been reported in the literature in individuals affected with LAMA4-related conditions. This variant is present in population databases (rs727503113, gnomAD 0.002%). This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 138 of the LAMA4 protein (p.His138Tyr). |
Gene |
RCV001762331 | SCV001999744 | uncertain significance | not provided | 2023-03-07 | criteria provided, single submitter | clinical testing | Identified in a patient with HCM in published literature (Burstein et al., 2021); this patient harbored additional cardiogenetic variants; Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 32746448) |
Ambry Genetics | RCV002326862 | SCV002632701 | uncertain significance | Cardiovascular phenotype | 2023-04-30 | criteria provided, single submitter | clinical testing | The p.H138Y variant (also known as c.412C>T), located in coding exon 3 of the LAMA4 gene, results from a C to T substitution at nucleotide position 412. The histidine at codon 138 is replaced by tyrosine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species; however, tyrosine 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. |