Submissions for variant NM_006940.6(SOX5):c.1672C>T (p.Arg558Cys)

dbSNP: rs1591908680

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000994877	SCV001148677	likely pathogenic	not provided	2019-08-01	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV003230613	SCV003929393	likely pathogenic	Lamb-Shaffer syndrome	2023-06-02	criteria provided, single submitter	clinical testing
Pittsburgh Clinical Genomics Laboratory, University of Pittsburgh Medical Center	RCV003230613	SCV005397458	likely pathogenic	Lamb-Shaffer syndrome	2023-01-06	criteria provided, single submitter	clinical testing	This sequence variant is a single nucleotide substitution (C>T) at coding position 1672 of the SOX5 gene that results in an arginine to cysteine amino acid change at residue 558 of the SOX5 protein. The Arg558 residue falls in the HMG domain which plays a critical role in SOX5-mediated transactivation (PMID: 31578471). This is a previously reported variant (ClinVar) that has been observed in an individual with Lamb-Shaffer syndrome (PMID: 33296143). This variant is absent from the gnomAD population database (0 of approximately 250,000 alleles). Multiple bioinformatic tools predict that this arginine to cysteine amino acid change would be damaging, and the Arg558 residue is strongly conserved across the vertebrate species examined. Studies examining the functiol consequence of this variant have not been published, to our knowledge. At this time, we consider this a likely pathogenic variant. ACMG Criteria: PM1, PM2, PP3, PS2