Submissions for variant NM_003106.4(SOX2):c.310G>T (p.Glu104Ter)

dbSNP: rs1260218988

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001267855	SCV004293541	pathogenic	Anophthalmia/microphthalmia-esophageal atresia syndrome	2023-08-23	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu104*) in the SOX2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 214 amino acid(s) of the SOX2 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with SOX2-related conditions (PMID: 18385794, 34367232). ClinVar contains an entry for this variant (Variation ID: 986764). This variant disrupts a region of the SOX2 protein in which other variant(s) (p.Tyr180*) have been determined to be pathogenic (PMID: 19921648). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Anophthalmia/Microphthalmia Research Registry, Einstein Medical Center Philadelphia	RCV001267855	SCV001446341	pathogenic	Anophthalmia/microphthalmia-esophageal atresia syndrome		no assertion criteria provided	research	Patient has symptoms similar to SOX2 related disease and is suspected to be pathogenic
Department of Rehabilitation Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea	RCV001267855	SCV004171817	pathogenic	Anophthalmia/microphthalmia-esophageal atresia syndrome		no assertion criteria provided	clinical testing