ClinVar Miner

Submissions for variant NM_000441.2(SLC26A4):c.2291C>T (p.Thr764Met)

gnomAD frequency: 0.00010  dbSNP: rs150597240
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Hearing Loss Variant Curation Expert Panel RCV000346954 SCV000840520 uncertain significance Pendred syndrome 2018-09-28 reviewed by expert panel curation The allele frequency of the p.Thr764Met variant in SLC26A4 is 0.01% (3/24024) of African alleles and 0.007% (9/126592) of European (Non-Finnish) alleles by the Genome Aggregation Database (http://gnomad.broadinstitute.org), which is a low enough frequency to award PM2_Supporting based on the thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss (PM2_P). However, rarity/absence alone does not support a pathogenic classification. In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: PM2_P.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000036482 SCV000060137 uncertain significance not specified 2012-07-25 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Thr764Met varia nt in SLC26A4 has not been reported in the literature nor previously identified by our laboratory. It has been identified in 0.01% (1/8600) of European America n chromosomes and 0.07% (3/4406) of African American chromosomes from a broad po pulation by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS /; dbSNP rs150597240), but this frequency is not high enough to rule out a patho genic role. Computational analyses (biochemical amino acid properties, conservat ion, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or agains t an impact to the protein. In summary, the clinical significance of this varian t cannot be determined without additional data.
Illumina Laboratory Services, Illumina RCV000289695 SCV000466109 uncertain significance Autosomal recessive nonsyndromic hearing loss 4 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina RCV000346954 SCV000466110 uncertain significance Pendred syndrome 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Fulgent Genetics, Fulgent Genetics RCV000764681 SCV000895812 uncertain significance Autosomal recessive nonsyndromic hearing loss 4; Pendred syndrome 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV001460836 SCV001664718 likely benign not provided 2024-01-10 criteria provided, single submitter clinical testing
Natera, Inc. RCV000346954 SCV001459945 uncertain significance Pendred syndrome 2020-09-16 no assertion criteria provided clinical testing

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