ClinVar Miner

Submissions for variant NM_000252.2(MTM1):c.1291G>A (p.Asp431Asn) (rs886044782)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000490085 SCV000332989 uncertain significance not provided 2017-05-16 criteria provided, single submitter clinical testing
GeneDx RCV000490085 SCV000577813 likely pathogenic not provided 2015-04-29 criteria provided, single submitter clinical testing The D431N variant in the MTM1 gene has been reported in a male patient affected with X-linked myotubular myopathy whose mother was noted to be a carrier (Laporte et al., 1997). The D431N variant was reported in cis with a second D433N variant, however the two missense variants are nearby and therefore would be considered as an insertion deletion alteration c.1291_1297delGATGCTGinsAATGCTA using alternate nomenclature. The D431N variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The D431N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. A missense variant in a nearby residue (R421Q) has been reported in the Human Gene Mutation Database in association with X-linked recessive myotubular myopathy (Stenson et al., 2014), supporting the functional importance of this region of the protein. The D431N variant is a strong candidate for a disease-causing variant, however the possibility it may be a rare benign variant cannot be excluded
Genetic Services Laboratory, University of Chicago RCV000304588 SCV000595862 uncertain significance not specified 2017-05-22 criteria provided, single submitter clinical testing

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