ClinVar Miner

Submissions for variant NM_003640.5(ELP1):c.947C>T (p.Pro316Leu) (rs374814563)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493897 SCV000583006 uncertain significance not provided 2017-05-18 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the IKBKAP gene. The P316L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The P316L variant is observed in 12/10,406 (0.1%) alleles from individuals of African background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P316L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, this substitution occurs at a position that is not conserved. In silico analysis predicts this variant likely does not alter 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.
Illumina Clinical Services Laboratory,Illumina RCV000302687 SCV000476583 uncertain significance Familial dysautonomia 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000493897 SCV000829353 uncertain significance not provided 2018-11-07 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 316 of the IKBKAP protein (p.Pro316Leu). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs374814563, ExAC 0.1%). This variant has not been reported in the literature in individuals with IKBKAP-related disease. ClinVar contains an entry for this variant (Variation ID: 364577). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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