ClinVar Miner

Submissions for variant NM_001105206.3(LAMA4):c.3122C>G (p.Ala1041Gly)

dbSNP: rs863223687
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000197744 SCV000250537 uncertain significance not provided 2014-07-11 criteria provided, single submitter clinical testing p.Ala1034Gly (GCC>GGC): c.3101 C>G in exon 24 of the LAMA4 gene (NM_002290.3). A variant of unknown significance has been identified in the LAMA4 gene. The A1034G variant has not been published as a mutation or as a benign polymorphism to our knowledge. The A1034G 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. In addition, this substitution occurs at a position that is completely conserved across species. Nevertheless, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.. Moreover, the A1034G variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. 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 RCV001371398 SCV001567959 uncertain significance Dilated cardiomyopathy 1JJ 2020-03-04 criteria provided, single submitter clinical testing 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. 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. This variant has not been reported in the literature in individuals with LAMA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 213592). This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with glycine at codon 1034 of the LAMA4 protein (p.Ala1034Gly). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and glycine.

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