ClinVar Miner

Submissions for variant NM_015884.4(MBTPS2):c.1286G>A (p.Arg429His)

dbSNP: rs122468178
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000081781 SCV000113716 pathogenic not provided 2012-07-23 criteria provided, single submitter clinical testing
GeneDx RCV000081781 SCV000321866 pathogenic not provided 2019-10-04 criteria provided, single submitter clinical testing Published functional studies demonstrate reduced enzymatic activity of the MBTPS2 protein, with variants such as R429H that are closer to the intramembranous domain being more detrimental than missense changes in the amino-terminal portion of the protein (Oeffner et al., 2009; Bornholdt et al; 2013); Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 19361614, 23316014, 22105905, 21179107, 27380894, 27663151, 26762237, 33258288)
3billion RCV000012157 SCV002058770 pathogenic IFAP syndrome 1, with or without BRESHECK syndrome 2022-01-03 criteria provided, single submitter clinical testing The variant has been observed in multiple (>3) similarly affected unrelated individuals(PMID: 19361614, 23316014, PS4_S). Functional studies provide strong evidence of the variant having a damaging effect on the gene or gene product (PMID: 19361614, 23316014, PS3_S). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.963, PP3_P). A missense variant is a common mechanism associated with IFAP syndrome with or without BRESHECK syndrome (PP2_P). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
OMIM RCV000012157 SCV000032391 pathogenic IFAP syndrome 1, with or without BRESHECK syndrome 2012-01-01 no assertion criteria provided literature only

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