ClinVar Miner

Submissions for variant NM_014140.4(SMARCAL1):c.1975C>T (p.Arg659Cys)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001305151 SCV001494473 uncertain significance Schimke immuno-osseous dysplasia 2020-10-09 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 659 of the SMARCAL1 protein (p.Arg659Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs148893764, ExAC 0.01%). This variant has been observed in individual(s) with focal segmental glomerulosclerosis (PMID: 28844315). 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.
Sydney Genome Diagnostics,Children's Hospital Westmead RCV001328268 SCV001449448 uncertain significance Atypical hemolytic uremic syndrome 2018-10-24 no assertion criteria provided clinical testing This patient is heterozygous for a variant of unknown clinical significance (VOUS), c.1975C>T p.(Arg659Cys), in exon 12 of the SMARCAL1 gene. To our knowledge, this variant has not been previously reported in the literature to be disease causing. This variant (dbSNP: rs148893764) has been reported in the ExAC database with a very low allele frequency (1 out of 121206 alleles). In silico analysis (Alamut Visual v2.6) using PolyPhen2, SIFT, Align GVGD and Mutation Taster all suggest that this variant to be likely pathogenic.

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