ClinVar Miner

Submissions for variant NM_000426.3(LAMA2):c.2462C>T (p.Thr821Met) (rs117422805)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000149994 SCV000196850 uncertain significance not specified 2017-06-21 criteria provided, single submitter clinical testing The T821M variant in the LAMA2 gene has been reported previously in the homozygous state in two siblings, from consanguineous parents, with congenital muscular dystrophy and abnormal white matter (Xiong et al., 2015). The T821M 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. In addition, this substitution alters a position that is conserved across species, and a missense variant at the same residue (T821P) has been reported in the Human Gene Mutation Database in two unrelated patients with atypical LAMA2-related disorders (Marques et al., 2014; Stenson et al., 2014). In silico analysis also predicts this variant is probably damaging to the protein structure/function. However, the T821M variant is observed in 24/6586 alleles (0.36%) from individuals of Finnish background, and 184/66,630 alleles (0.28%) from individuals of non-Finnish European background, in the ExAC dataset with 2 homozygous South Asian control individuals reported (Lek et al., 2016). Therefore, we interpret T821M as a variant of uncertain significance.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000723613 SCV000331387 uncertain significance not provided 2015-06-22 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV000149994 SCV000595502 uncertain significance not specified 2016-09-24 criteria provided, single submitter clinical testing
Invitae RCV001084610 SCV000658653 benign Laminin alpha 2-related dystrophy 2019-12-31 criteria provided, single submitter clinical testing
Counsyl RCV000670870 SCV000795783 uncertain significance Merosin deficient congenital muscular dystrophy 2017-11-25 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001156369 SCV001317862 uncertain significance Congenital muscular dystrophy due to partial LAMA2 deficiency 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille RCV001252050 SCV001427798 likely benign Intellectual disability 2019-01-01 no assertion criteria provided clinical testing

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