Submissions for variant NM_000441.2(SLC26A4):c.1363A>T (p.Ile455Phe)

gnomAD frequency: 0.00003  dbSNP: rs375576481

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Hearing Loss Variant Curation Expert Panel	RCV000710343	SCV000840540	benign	Pendred syndrome	2018-09-28	reviewed by expert panel	curation	The filtering allele frequency of the p.Ile455Phe variant in the SLC26A4 gene is 3% (981/30778) of South Asian chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org; calculated by using inverse allele frequency at https://www.cardiodb.org/allelefrequencyapp/), which is a high frequency that is consistent with benign classification based on thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss variants (BA1).
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036441	SCV000060096	benign	not specified	2016-03-03	criteria provided, single submitter	clinical testing	p.Ile455Phe in exon 12 of SLC26A4: This variant is not expected to have clinical significance because it has been identified in 3.2% (520/16506) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitut e.org; dbSNP rs375576481).
Eurofins Ntd Llc (ga)	RCV000036441	SCV000225516	benign	not specified	2015-01-16	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000441541	SCV000511788	benign	not provided	2017-01-24	criteria provided, single submitter	clinical testing
GeneDx	RCV000441541	SCV000977459	benign	not provided	2018-03-30	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV000441541	SCV001041168	benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000710343	SCV001324678	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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001162716	SCV001324679	uncertain significance	Autosomal recessive nonsyndromic hearing loss 4	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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001258258	SCV001435172	benign	Microcephaly 5, primary, autosomal recessive		criteria provided, single submitter	research	The p.Ile455Phe variant in SLC26A4 has been identified in at least 2 individuals with non-syndromic deafness (PMID: 12676893), and has been identified in >3% of South Asian chromosomes and 13 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as benign for autosomal recessive non-syndromic deafness.
Fulgent Genetics, Fulgent Genetics	RCV002496560	SCV002805334	likely benign	Autosomal recessive nonsyndromic hearing loss 4; Pendred syndrome	2022-05-05	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000710343	SCV001459871	benign	Pendred syndrome	2020-04-16	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000036441	SCV001917618	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000441541	SCV001968386	likely benign	not provided		no assertion criteria provided	clinical testing