Submissions for variant NM_000441.2(SLC26A4):c.2211G>C (p.Glu737Asp)

gnomAD frequency: 0.00030  dbSNP: rs200664061

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000154323	SCV000203985	uncertain significance	not specified	2017-04-25	criteria provided, single submitter	clinical testing	The p.Glu737Asp variant in SLC26A4 has been previously reported in four individu als with hearing loss, one of whom had no inner ear abnormalities. It was not re ported for the remaining three individuals whether or not inner ear abnormalitie s were present (Dai 2009, LMM unpublished data). All these individuals were hete rozygous for this variant and a second pathogenic variant was not identified. Th is variant has been identified in 17/111562 European chromosomes by the Genome A ggregation Database (gnomAD, http://http://gnomad.broadinstitute.org; dbSNP rs20 0664061); however this frequency is not high enough to rule out a pathogenic rol e. A functional study reported that the p.Glu737Asp variant, when expressed in X enopus oocytes, had a reduced rate of Cl(-)/HCO(3)(-) exchange (Dai 2009), thoug h this in vitro assay may not accurately represent biological function. Computat ional prediction tools and conservation analyses suggest that the Glu737Asp vari ant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of the p.Glu73 7Asp variant is uncertain.
Counsyl	RCV000671675	SCV000796672	uncertain significance	Pendred syndrome	2017-12-28	criteria provided, single submitter	clinical testing
Invitae	RCV000945063	SCV001091049	likely benign	not provided	2024-01-29	criteria provided, single submitter	clinical testing
Department of Otolaryngology – Head & Neck Surgery, Cochlear Implant Center	RCV001375309	SCV001571931	uncertain significance	Hearing impairment	2021-04-12	criteria provided, single submitter	clinical testing	PM2_Supporting, BP4_Supporting
Genome-Nilou Lab	RCV001785479	SCV002027484	uncertain significance	Autosomal recessive nonsyndromic hearing loss 4	2021-09-05	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000671675	SCV002027495	uncertain significance	Pendred syndrome	2021-09-05	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000945063	SCV003917547	uncertain significance	not provided	2023-02-01	criteria provided, single submitter	clinical testing	SLC26A4: PM2, BP4