ClinVar Miner

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

gnomAD frequency: 0.00001  dbSNP: rs148893764
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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 RCV001305151 SCV001494473 uncertain significance Schimke immuno-osseous dysplasia 2022-10-24 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 659 of the SMARCAL1 protein (p.Arg659Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with focal segmental glomerulosclerosis (PMID: 28844315). ClinVar contains an entry for this variant (Variation ID: 988238). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SMARCAL1 protein function. 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.
Natera, Inc. RCV001305151 SCV002076316 uncertain significance Schimke immuno-osseous dysplasia 2020-03-27 no assertion criteria provided clinical testing

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