ClinVar Miner

Submissions for variant NM_001105206.3(LAMA4):c.2342C>A (p.Ala781Asp)

dbSNP: rs863223685
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000197420 SCV000250531 uncertain significance not provided 2014-04-15 criteria provided, single submitter clinical testing p.Ala774Asp (GCT>GAT): c.2321 C>A in exon 18 of the LAMA4 gene (NM_002290.3). A variant of unknown significance has been identified in the LAMA4 gene. The A774D variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The A774D variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The A774D variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. This variant was found in CARDIOMYOPATHY
Invitae RCV001857721 SCV002212955 uncertain significance Dilated cardiomyopathy 1JJ 2021-03-11 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with LAMA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 213586). This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with aspartic acid at codon 774 of the LAMA4 protein (p.Ala774Asp). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and aspartic acid.

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