ClinVar Miner

Submissions for variant NM_000426.3(LAMA2):c.5598G>T (p.Met1866Ile) (rs1554289926)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000498641 SCV000590043 uncertain significance not specified 2017-06-07 criteria provided, single submitter clinical testing The M1866I variant in the LAMA2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The M1866I variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). However, the M1866I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. 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 M1866I as a variant of uncertain significance.
Geisinger Autism and Developmental Medicine Institute,Geisinger Health System RCV000678265 SCV000804320 uncertain significance Merosin deficient congenital muscular dystrophy 2017-06-30 criteria provided, single submitter provider interpretation This 5 year old female has a history of global developmental delay, hypotonia, plagiocephaly, and abnormalities of blood clotting, and is compound heterozygous for variants in the LAMA2 gene. Compound heterozygous or homozygous LAMA2 variants are associated with a spectrum of muscular dystrophy phenotypes from severe, early-onset congenital muscular dystrophy to a milder later childhood onset limb-girdle muscular dystrophy. The c.5598G>T variant is absent from population databases (ExAC and gnomAD). Computational models are inconsistent. Follow-up testing showed mildly elevated CK levels 212 (reference range 26-192).

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