ClinVar Miner

Submissions for variant NM_002180.2(IGHMBP2):c.1616C>T (p.Ser539Leu) (rs879253887)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235493 SCV000292588 uncertain significance not provided 2018-10-02 criteria provided, single submitter clinical testing The S539L variant has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 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 S539L 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 across species, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Service de Pédiatrie - Neurologie et infectiologie - Toulouse,CHU de Toulouse - Hôpital des Enfants RCV000677264 SCV000681405 likely pathogenic Spinal muscular atrophy, distal, autosomal recessive, 1 2016-08-17 criteria provided, single submitter clinical testing 6 typical cases of SMARD1 were observed with an homozygous mutation at this location. Although it is a missense mutation on a poorly conserved portion of DNA across species, it involves the main functional domain of the protein IGHMBP 2 the DNA helicase domain, on a specific region where ATP binding sites seems to be concentrated (region 2A).

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