ClinVar Miner

Submissions for variant NM_001105206.3(LAMA4):c.153C>A (p.Ser51Arg)

gnomAD frequency: 0.00001  dbSNP: rs782192817
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Total submissions: 4
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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, 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, LabCorp 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.

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