Submissions for variant NM_014140.4(SMARCAL1):c.2263A>G (p.Ile755Val)

gnomAD frequency: 0.00005  dbSNP: rs578123335

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001035294	SCV001198618	uncertain significance	Schimke immuno-osseous dysplasia	2022-09-27	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 755 of the SMARCAL1 protein (p.Ile755Val). This variant is present in population databases (rs578123335, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with SMARCAL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 834577). 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 not 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.
Fulgent Genetics, Fulgent Genetics	RCV001035294	SCV002790351	uncertain significance	Schimke immuno-osseous dysplasia	2022-04-10	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV002511018	SCV002821026	uncertain significance	not provided	2022-11-01	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001035294	SCV002076324	uncertain significance	Schimke immuno-osseous dysplasia	2020-03-24	no assertion criteria provided	clinical testing