ClinVar Miner

Submissions for variant NM_000426.3(LAMA2):c.3244C>T (p.His1082Tyr) (rs146490004)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413698 SCV000491767 uncertain significance not specified 2016-11-11 criteria provided, single submitter clinical testing The H1082Y variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The H1082Y 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 where amino acids with similar properties to Histidine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Invitae RCV000557605 SCV000658665 uncertain significance Laminin alpha 2-related dystrophy 2019-10-04 criteria provided, single submitter clinical testing This sequence change replaces histidine with tyrosine at codon 1082 of the LAMA2 protein (p.His1082Tyr). The histidine residue is weakly conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is present in population databases (rs146490004, ExAC 0.03%) but has not been reported in the literature in individuals with a LAMA2-related disease. 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. In summary, this variant is a rare missense change that is not predicted to affect protein function, and is found in the population at an appreciable frequency. This variant is not anticipated to cause disease; however, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics,Fulgent Genetics RCV000764623 SCV000895731 uncertain significance Merosin deficient congenital muscular dystrophy; MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 23 2018-10-31 criteria provided, single submitter clinical testing
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille RCV001252052 SCV001427800 uncertain significance Intellectual disability 2019-01-01 no assertion criteria provided clinical testing

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