Submissions for variant NM_000441.2(SLC26A4):c.164+1del

dbSNP: rs786204504

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000169187	SCV000220430	likely pathogenic	Pendred syndrome	2014-06-19	criteria provided, single submitter	literature only
Labcorp Genetics (formerly Invitae), Labcorp	RCV001040907	SCV001204498	pathogenic	not provided	2021-05-14	criteria provided, single submitter	clinical testing	This variant has been observed in individual(s) with clinical features of Pendred syndrome (PMID: 22717225, 27861301). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as IVS2+1delG. ClinVar contains an entry for this variant (Variation ID: 188838). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change creates a premature translational stop signal (p.Ser55Ilefs*11) in the SLC26A4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC26A4 are known to be pathogenic (PMID: 16283880, 25394566, 26252218, 26445815). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab	RCV000169187	SCV002026520	likely pathogenic	Pendred syndrome	2021-09-05	criteria provided, single submitter	clinical testing
Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin	RCV003330085	SCV004037138	pathogenic	Autosomal recessive nonsyndromic hearing loss 4		criteria provided, single submitter	not provided
Baylor Genetics	RCV003330085	SCV004204212	pathogenic	Autosomal recessive nonsyndromic hearing loss 4	2023-02-22	criteria provided, single submitter	clinical testing
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV001040907	SCV005198264	pathogenic	not provided	2023-09-25	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000169187	SCV002079962	pathogenic	Pendred syndrome	2021-07-29	no assertion criteria provided	clinical testing
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas	RCV003330085	SCV004041807	pathogenic	Autosomal recessive nonsyndromic hearing loss 4	2023-10-09	no assertion criteria provided	clinical testing