ClinVar Miner

Submissions for variant NM_003640.5(ELP1):c.3869A>G (p.Asn1290Ser) (rs145319352)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000355008 SCV000476541 uncertain significance Familial dysautonomia 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000757404 SCV000618672 uncertain significance not provided 2017-07-05 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the IKBKAP gene. The N1290S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The N1290S variant is observed in 30/10398 (0.3%) alleles from individuals of African background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The N1290S variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. However, 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000757404 SCV000885610 uncertain significance not provided 2017-06-14 criteria provided, single submitter clinical testing The p.Asn1290Ser variant (rs145319352) has not been reported in the medical literature, nor has it been previously identified in our laboratory; however, it is listed in the ClinVar database as a variant of uncertain significance (Variation ID: 364552). It is listed in the Genome Aggregation Database (gnomAD) browser with a frequency in African populations of 0.30% (identified in 71 out of 24,036 chromosomes). The asparagine at codon 1290 is moderately conserved (Alamut software v2.9), however several species of rodent, in addition to other species of mammal, have a serine at this position, suggesting this change is evolutionary tolerated. Furthermore, computational analyses suggest this variant does not have a significant effect on IKBKAP protein structure/function (SIFT: tolerated, PolyPhen2: benign, and Mutation Taster: polymorphism). However, based on the available information, the clinical significance of the p.Asn1290Ser variant cannot be determined with certainty.
Invitae RCV000757404 SCV001004923 likely benign not provided 2019-02-15 criteria provided, single submitter clinical testing

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