Submissions for variant NM_006940.6(SOX5):c.637C>T (p.Arg213Ter)

dbSNP: rs767241917

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000599067	SCV000710042	pathogenic	not provided	2024-08-15	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 36861937, 34015165)
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV000656421	SCV000778431	likely pathogenic	Lamb-Shaffer syndrome	2017-06-29	criteria provided, single submitter	clinical testing
Genetics and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University	RCV000656421	SCV001622436	pathogenic	Lamb-Shaffer syndrome	2021-05-13	criteria provided, single submitter	clinical testing
Lifecell International Pvt. Ltd	RCV000656421	SCV003922075	pathogenic	Lamb-Shaffer syndrome		criteria provided, single submitter	clinical testing	A Heterozygous Nonsense variant c.637C>T in Exon 5 of the SOX5 gene that results in the amino acid substitution p.Arg213* was identified. The observed is novel in gnomAD exomes and genomes. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score . Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. ClinVar has also classified this variant as Pathogenic [Variant ID : 503755]. The observed variation has previously been reported for Lamb–Shaffer syndrome by Zawerton, Ash, et al. , 2020. For these reasons this variant has been classified as Pathogenic .
Molecular Genetics Lab, CHRU Brest	RCV000656421	SCV004697723	pathogenic	Lamb-Shaffer syndrome		criteria provided, single submitter	clinical testing
Institute for Human Genetics, University Hospital Essen	RCV000656421	SCV000999884	pathogenic	Lamb-Shaffer syndrome	2019-08-05	no assertion criteria provided	clinical testing