ClinVar Miner

Submissions for variant NM_004260.3(RECQL4):c.2099T>C (p.Leu700Pro) (rs563222200)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000498056 SCV000590557 uncertain significance not provided 2017-06-21 criteria provided, single submitter clinical testing The L700P variant in the RECQL4 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant is observed in 7/8180 (0.085%) alleles from individuals of South Asian background in the ExAC dataset (Lek et al., 2016). The L700P variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret L700P as a variant of uncertain significance.
Invitae RCV000233140 SCV000288206 uncertain significance Baller-Gerold syndrome 2018-07-18 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 700 of the RECQL4 protein (p.Leu700Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is present in population databases (rs563222200, ExAC 0.09%). This variant has not been reported in the literature in individuals with RECQL4-related disease. ClinVar contains an entry for this variant (Variation ID: 239715). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but 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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