ClinVar Miner

Submissions for variant NM_004260.3(RECQL4):c.3061C>T (p.Arg1021Trp) (rs137853232)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000006445 SCV000631147 pathogenic Baller-Gerold syndrome 2018-12-06 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 1021 of the RECQL4 protein (p.Arg1021Trp). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs137853232, ExAC 0.02%). This variant has been observed in combination with, and on the opposite chromosome (in trans) from, pathogenic variants in RECQL4 in individuals affected with Baller-Gerold syndrome and Rothmund-Thomson syndrome (PMID: 15897384, 15964893, 23899764, 24635570). In a single family, this variant was shown to segregate with disease in at least two of the affected family members (PMID: 15964893). These findings are consistent with autosomal recessive inheritance, and suggest that this variant contributes to disease. This variant is also referred to as g.5435C>T in the literature. ClinVar contains an entry for this variant (Variation ID: 6073). 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 arginine 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. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000006445 SCV000026628 pathogenic Baller-Gerold syndrome 2009-02-01 no assertion criteria provided literature only

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