ClinVar Miner

Submissions for variant NM_000441.2(SLC26A4):c.1924T>C (p.Ser642Pro) (rs397516423)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Hearing Loss Variant Curation Expert Panel RCV001004781 SCV001164265 uncertain significance Pendred syndrome 2019-09-25 reviewed by expert panel curation The filtering allele frequency of the p.Ser642Pro variant in SLC26A4 is 0.467% (188/35420) for Latino chromosomes in gnomAD (BS1). The variant has been detected with another pathogenic SLC26A4 variant with unknown phase in 1 proband with sensorineural hearing loss and enlarged vestibular aqueducts (PM3_Supporting, PP4, SCV000060117.6, Laboratory for Molecular Medicine internal data). Additionally, computational prediction tools and conservation analysis suggest that the p.Ser642Pro variant may impact the protein (PP3). In summary, due to conflicting evidence, this variant has been classified as uncertain for autosomal recessive Pendred syndrome. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: BS1, PM3_Supporting, PP4, PP3.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000036462 SCV000060117 uncertain significance not specified 2018-06-08 criteria provided, single submitter clinical testing The p.Ser642Pro variant in SLC26A4 has been previously identified by our laborat ory in three Hispanic individuals with hearing loss, one of whom had a second pa thogenic SLC26A4 variant and was reported to have EVA. This variant has been ide ntified in 0.5% (175/34396) of Latino chromosomes by the Genome Aggregation Data base (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs397516423), which is a f requency high enough to suggest that it may be benign. Computational prediction tools and conservation analyses suggest that this variant may impact the protein , though this information is not predictive enough to determine pathogenicity. I n summary, the clinical significance of this variant is uncertain. ACMG/AMP crit eria applied: PM3, PP3, PP4, BS1.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000036462 SCV000345424 likely benign not specified 2016-09-07 criteria provided, single submitter clinical testing
Invitae RCV000966198 SCV001113490 likely benign not provided 2020-12-04 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001004781 SCV001321633 uncertain significance Pendred syndrome 2017-04-28 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 RCV001159887 SCV001321634 uncertain significance Deafness, autosomal recessive 4, with enlarged vestibular aqueduct 2017-04-28 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.

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