ClinVar Miner

Submissions for variant NM_000441.2(SLC26A4):c.916dup (p.Val306fs) (rs768245266)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000409855 SCV000485440 likely pathogenic Pendred syndrome 2015-12-11 criteria provided, single submitter clinical testing
Invitae RCV000812506 SCV000952821 pathogenic not provided 2018-12-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val306Glyfs*24) in the SLC26A4 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs768245266, ExAC 0.02%). This variant has been observed in individuals affected with non-syndromic hearing loss and Pendred syndrome (PMID: 14715652, 17718863, 21366435, 26252218). It is also known as 916_917insG and 916insG in the literature. ClinVar contains an entry for this variant (Variation ID: 370192). Loss-of-function variants in SLC26A4 are known to be pathogenic (PMID: 16283880, 25394566, 26252218, 26445815). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000812506 SCV001167878 pathogenic not provided 2020-06-22 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; Published functional studies demonstrate a damaging effect on iodide transport (Gillam et al., 2004); This variant is associated with the following publications: (PMID: 30275481, 30896630, 31827275, 31581539, 30842343, 26252218, 14715652, 27240500, 20483489, 23302201, 17718863)
Victorian Clinical Genetics Services,Murdoch Childrens Research Institute RCV001089561 SCV001244770 pathogenic Deafness, autosomal recessive 4, with enlarged vestibular aqueduct 2017-10-27 criteria provided, single submitter clinical testing A heterozygous duplication variant, NM_000441.1(SLC26A4):c.916dupG, has been identified in exon 7 of 21 of the SLC26A4 gene. This variant is predicted to cause a frameshift from amino acid position 306 and introduce a stop codon 24 residues downstream, NP_000432.1(SLC26A4):p.(Val306Glyfs*24), resulting in loss of protein function either through truncation (involving half of the protein including functional domains) or nonsense-mediated decay.This variant is present in the gnomAD database with a global frequency of 0.0014% (2 in 277028, 0 homozygotes) and in East Asian populations at a frequency of 0.02% (4 in 18862, 0 homozygotes). The variant has been previously described as pathogenic in multiple families withsevere to profoundhearing loss(ClinVar, Li, Q. et al. (2012), Lee, HJ. et al. (2014),Mori, al. (2016), Wang, Q-J. et al. (2007),Jung, J. et al. (2017)). Based on current informationthis variant has been classified as PATHOGENIC.

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