ClinVar Miner

Submissions for variant NM_015272.5(RPGRIP1L):c.1156A>G (p.Lys386Glu) (rs137982921)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724780 SCV000225033 uncertain significance not provided 2015-04-30 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765297 SCV000896552 uncertain significance COACH syndrome; Joubert syndrome 7; Meckel syndrome type 5 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000724780 SCV000567316 uncertain significance not provided 2018-08-29 criteria provided, single submitter clinical testing The K386E variant in the RPGRIP1L gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. Although not present in the homozygous state, the K386E variant is observed in 82/66610 (0.23%) alleles from individuals of non-Finnish European background, in the ExAC dataset (Lek et al., 2016). The K386E 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. This substitution occurs at a position where amino acids with similar properties to Lysine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret K386E as a variant of uncertain significance.
Illumina Clinical Services Laboratory,Illumina RCV000339807 SCV000397832 uncertain significance Meckel-Gruber syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000401583 SCV000397833 uncertain significance Joubert syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000307599 SCV000397834 uncertain significance Nephronophthisis 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000697464 SCV000826076 uncertain significance Joubert syndrome; Meckel-Gruber syndrome 2018-03-02 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamic acid at codon 386 of the RPGRIP1L protein (p.Lys386Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is present in population databases (rs137982921, ExAC 0.1%). This variant has been reported in an individual affected with Jourbert syndrome, however no other variant in RPGRIP1L was identified (PMID: 23188109). ClinVar contains an entry for this variant (Variation ID: 193717). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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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