Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000469423 | SCV000544602 | uncertain significance | Dilated cardiomyopathy 1JJ | 2023-12-21 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 51 of the LAMA4 protein (p.Ser51Arg). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with LAMA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 406145). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. |
Fulgent Genetics, |
RCV000469423 | SCV002777169 | uncertain significance | Dilated cardiomyopathy 1JJ | 2021-08-09 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV003372717 | SCV004096747 | uncertain significance | Cardiovascular phenotype | 2023-07-30 | criteria provided, single submitter | clinical testing | The p.S51R variant (also known as c.153C>A), located in coding exon 1 of the LAMA4 gene, results from a C to A substitution at nucleotide position 153. The serine at codon 51 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003401458 | SCV004122737 | uncertain significance | not specified | 2023-10-11 | criteria provided, single submitter | clinical testing | Variant summary: LAMA4 c.153C>A (p.Ser51Arg) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.5e-05 in 198640 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.153C>A in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |