ClinVar Miner

Submissions for variant NM_000441.2(SLC26A4):c.147C>G (p.Ser49Arg) (rs756969021)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Hearing Loss Variant Curation Expert Panel RCV001004774 SCV001164256 likely benign Pendred syndrome 2019-10-02 reviewed by expert panel curation The SLC26A4 p.Ser49Arg variant has been identified in a heterozygous state in two Chinese individuals with congenital non-syndromic hearing loss (PMID: 25149764). No information about segregation of the variant or whether it was in trans with another SLC26A4 variant was given. The filtering allele frequency of the p.Ser49Arg variant in the SLC26A4 gene is 0.27% for East Asian chromosomes by gnomAD (44/12282 with 95% CI), which is a higher frequency than would be expected for an autosomal recessive pathogenic variant based on the thresholds defined by the ClinGen Hearing Loss Expert Panel (BS1_Supporting). Additionally, computational prediction analysis using the metapredictor tool REVEL suggests that the variant may not impact the protein (BP4). Splice prediction analysis using MaxEntScan does not suggest an impact to splicing (BP4). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel : BS1_Supporting, BP4.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000221470 SCV000270849 likely benign not specified 2015-11-05 criteria provided, single submitter clinical testing p.Ser49Arg in exon 2 of SLC26A4: This variant is not expected to have clinical s ignificance due to a lack of conservation across species, including mammals. Of note, >10 mammals have an Arginine (Arg) at this position.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000726317 SCV000343753 uncertain significance not provided 2016-08-03 criteria provided, single submitter clinical testing
Invitae RCV000726317 SCV001084708 likely benign not provided 2020-11-02 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001004774 SCV001326718 uncertain significance Pendred syndrome 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001004619 SCV001326719 uncertain significance Deafness, autosomal recessive 4, with enlarged vestibular aqueduct 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
National Institute of Sensory Organs,National Hospital Organization Tokyo Medical Center RCV001004619 SCV000994859 other Deafness, autosomal recessive 4, with enlarged vestibular aqueduct 2019-08-20 no assertion criteria provided clinical testing Benign effect in vitro experiment
The Core Laboratory in Medical Center of Clinical Research,Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine RCV001004774 SCV001438731 benign Pendred syndrome 2020-05-12 no assertion criteria provided clinical testing
Natera, Inc. RCV001004774 SCV001455792 likely benign Pendred syndrome 2020-09-16 no assertion criteria provided clinical testing

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