ClinVar Miner

Submissions for variant NM_001023570.4(IQCB1):c.1000A>C (p.Lys334Gln)

gnomAD frequency: 0.00006  dbSNP: rs532987681
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002001416 SCV002274473 uncertain significance Nephronophthisis 2022-06-09 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 334 of the IQCB1 protein (p.Lys334Gln). This variant is present in population databases (rs532987681, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with IQCB1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; 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.
Fulgent Genetics, Fulgent Genetics RCV002479687 SCV002779065 uncertain significance Senior-Loken syndrome 5 2022-04-24 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV002479687 SCV005438786 uncertain significance Senior-Loken syndrome 5 2023-07-22 criteria provided, single submitter clinical testing The observed missense c.1000A>C p.Lys334Gln variant in IQCB1 gene has been reported previously in an individual affected with anterior segment dysgeneses Cheong et al., 2016. The p.Lys334Gln variant is present with allele frequency of 0.01% in gnomAD Exomes. This variant has been submitted to the ClinVar database as Uncertain Significance. Computational evidence Polyphen - Probably Damaging, SIFT - Tolerated and MutationTaster - Disease causing predicts conflicting evidence on protein structure and function for this variant. The reference amino acid of p.Lys334Gln in IQCB1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Lys at position 334 is changed to a Gln changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as a Variant of Uncertain Significance VUS. In absence of another reportable variant in IQCB1 gene, the molecular diagnosis is not confirmed.

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