Submissions for variant NM_000441.2(SLC26A4):c.1341+1del

dbSNP: rs397516417

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036439	SCV000060094	pathogenic	Rare genetic deafness	2014-05-20	criteria provided, single submitter	clinical testing	The c.1341+1delG variant in SLC26A4 has been reported in 5 probands with DFNB4/P endred syndrome, and segregated with hearing loss in 7 affected relatives in 2 f amilies (Everett 1997, Shahin 2010, Sheffield 1996, Tekin 2003, LMM unpublished data). Four out of 5 probands were homozygous or compound heterozygous. This var iant occurs in the invariant region (+/- 1/2) of the splice consensus sequence a nd is predicted to cause altered splicing leading to an abnormal or absent prote in. In summary, the c.1341+1delG variant meets our criteria to be classified as pathogenic (http://www.partners.org/personalizedmedicince/LMM).
King Laboratory, University of Washington	RCV001807761	SCV002059888	pathogenic	Autosomal recessive nonsyndromic hearing loss 4	2020-08-01	criteria provided, single submitter	research	Analysis of patient-derived RNA indicates that SLC26A4 c.1341+1delG disrupts the splice donor of exon 11, with loss of 78bp in message and loss of aa 422-446, a complete transmembrane domain (Abu Rayyan 2020). The variant is compound heterozygous with SLC26A4 c.1149_1149+5 in 4 Palestinian children with severe to profound pre-lingual hearing loss and EVA. It is absent from 1300 Palestinian controls and from gnomAD v2.1.1.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001852760	SCV002200653	pathogenic	not provided	2021-12-11	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 43505). This variant is also known as c.1341+1del, 1565delG, or 1565+1delG. This premature translational stop signal has been observed in individual(s) with SLC26A4-related conditions (PMID: 9398842, 19888295, 28964290). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys447Asnfs*8) 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).
Baylor Genetics	RCV001807761	SCV004204220	pathogenic	Autosomal recessive nonsyndromic hearing loss 4	2023-02-01	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV001807761	SCV005374087	pathogenic	Autosomal recessive nonsyndromic hearing loss 4	2024-09-22	criteria provided, single submitter	clinical testing
OMIM	RCV000454189	SCV000025258	pathogenic	Pendred syndrome	1997-12-01	no assertion criteria provided	literature only
Hereditary Research Laboratory, Bethlehem University	RCV000454189	SCV000538117	pathogenic	Pendred syndrome	2016-06-04	no assertion criteria provided	research	Severe to Profound SNHL
Hereditary Research Laboratory, Bethlehem University	RCV000454189	SCV000538120	pathogenic	Pendred syndrome	2016-06-04	no assertion criteria provided	research	severe to profound w/endolymphatic sac