Submissions for variant NM_000441.2(SLC26A4):c.2127del (p.Phe709fs)

dbSNP: rs786204523

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000169223	SCV000220488	likely pathogenic	Pendred syndrome	2014-07-08	criteria provided, single submitter	literature only
Invitae	RCV001208827	SCV001380236	pathogenic	not provided	2024-01-04	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Phe709Leufs*12) 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). This variant is present in population databases (rs558570919, gnomAD 0.002%). This premature translational stop signal has been observed in individuals with Pendred syndrome (PMID: 9618167, 24224479). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 188869). For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab	RCV000169223	SCV002026969	likely pathogenic	Pendred syndrome	2021-09-05	criteria provided, single submitter	clinical testing
GeneDx	RCV001208827	SCV002770055	pathogenic	not provided	2022-06-22	criteria provided, single submitter	clinical testing	Frameshift 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: 24224479, 33199029, 9618167)
Baylor Genetics	RCV003474900	SCV004201839	pathogenic	Autosomal recessive nonsyndromic hearing loss 4	2024-03-10	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000169223	SCV002080025	pathogenic	Pendred syndrome	2020-07-17	no assertion criteria provided	clinical testing