ClinVar Miner

Submissions for variant NM_000426.3(LAMA2):c.5291A>G (p.Glu1764Gly) (rs141950826)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000712189 SCV000590517 uncertain significance not provided 2017-06-22 criteria provided, single submitter clinical testing The E1764G variant in the LAMA2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The E1764G variant is observed in 3/11442 (0.026%) alleles from individuals of Latino background, in the ExAC dataset, and no individuals were reported to be homozygous (Lek et al., 2016). The E1764G 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. However, this substitution occurs at a position that is not conserved and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret E1764G as a variant of uncertain significance.
Invitae RCV000689906 SCV000817576 uncertain significance Laminin alpha 2-related dystrophy 2018-10-16 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glycine at codon 1764 of the LAMA2 protein (p.Glu1764Gly). The glutamic acid residue is weakly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is present in population databases (rs141950826, ExAC 0.03%). This variant has not been reported in the literature in individuals with LAMA2-related disease. ClinVar contains an entry for this variant (Variation ID: 432756). 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 tolerated, 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.
Athena Diagnostics Inc RCV000712189 SCV000842621 uncertain significance not provided 2018-08-22 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000712189 SCV001335151 uncertain significance not provided 2020-03-01 criteria provided, single submitter clinical testing

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