ClinVar Miner

Submissions for variant NM_001065.4(TNFRSF1A):c.935G>A (p.Arg312Lys) (rs200900510)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001703505 SCV000514913 likely benign not provided 2021-05-12 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 28814775)
Invitae RCV000537537 SCV000637238 benign TNF receptor-associated periodic fever syndrome (TRAPS) 2020-12-06 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282293 SCV001157935 uncertain significance none provided 2020-03-10 criteria provided, single submitter clinical testing The TNFRSF1A c.935G>A; p.Arg312Lys variant (rs200900510) is reported in the medical literature in an individual with Behcet disease (Burillo-Sanz 2017). The variant is reported in the ClinVar database (Variation ID: 378735) and is listed in the African population with an allele frequency of 0.35% (69/19,970 alleles, including 1 homozygote) in the Genome Aggregation Database. The arginine at this position is moderately conserved and computational algorithms (PolyPhen-2, SIFT) predict this variant is tolerated. Additionally, there are few known pathogenic variants in this region of the protein (Lobito 2011). Based on this and the increased population frequency in the African population, it is unlikely that this is a high penetrance pathogenic variant. However, we cannot rule out the possibility that this is a low penetrance variant without additional information. Therefore, considering available information, this variant is classified as a variant of uncertain significance. References: Burillo-Sanz S et al. Mutational profile of rare variants in inflammasome-related genes in Behcet disease: A Next Generation Sequencing approach. Sci Rep. 2017 Aug 16;7(1):8453. Lobito AA et al. Disease causing mutations in the TNF and TNFR superfamilies: Focus on molecular mechanisms driving disease. Trends Mol Med. 2011 Sep;17(9):494-505.
Illumina Clinical Services Laboratory,Illumina RCV000537537 SCV001267911 likely benign TNF receptor-associated periodic fever syndrome (TRAPS) 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Department of Immunology,Hospital Universitario Virgen del Rocio RCV000458191 SCV000503001 pathogenic Behcet disease 2017-02-22 no assertion criteria provided case-control

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