Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000036440 | SCV000060095 | pathogenic | Rare genetic deafness | 2012-04-27 | criteria provided, single submitter | clinical testing | The 1342-2_1343dupAGTC variant in SLC26A4 has been reported as a compound hetero zygous variant in 3 individuals with enlarged vestibular aqueducts (EVA) and has been identified by our laboratory in 3 other individuals each of whom has a sec ond pathogenic SLC26A4 variant (Choi 2009, LMM unpublished data). This variant l eads to the duplication of a conserved splice site at the beginning of exon 12, which could either deleteriously affect splicing of the transcript or cause a fr ameshift if 4 additional bases are included in the exon. In summary, this varian t meets our criteria to be classified as pathogenic (http://pcpgm.partners.org/L MM). |
| Labcorp Genetics |
RCV001248593 | SCV001422092 | pathogenic | not provided | 2024-08-12 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 11 of the SLC26A4 gene. It does not directly change the encoded amino acid sequence of the SLC26A4 protein. This variant is present in population databases (rs756270039, gnomAD 0.009%). This variant has been observed in individuals with deafness with enlargement of the vestibular aqueduct (PMID: 15689455, 19204907). This variant is also known as c.1342-2_1343dup (p.Leu450Glyfs*19) if splicing occurs at the native splice site. It is also referred to as c.1340_1343dup and 1343–1344insAGTC in the literature. ClinVar contains an entry for this variant (Variation ID: 43506). For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV001248593 | SCV001824770 | pathogenic | not provided | 2023-06-19 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense-mediated mRNA decay in a gene for which loss-of-function is a known mechanism of disease; In silico analysis supports that this variant does not alter splicing; This variant is associated with the following publications: (PMID: 19204907, 21704276, 31589614, 15689455) |
| Prevention |
RCV004534762 | SCV004116776 | pathogenic | SLC26A4-related disorder | 2023-02-11 | criteria provided, single submitter | clinical testing | The SLC26A4 c.1342-2_1343dupAGTC variant is predicted to result in a duplication affecting a canonical splice site. This variant has been reported along with a second SLC26A4 variant in individuals with an enlarged vestibular aqueduct (described as 1343-1344insAGTC in Pryor et al. 2005. PubMed ID: 15689455; described as c.1340_1343dup in Choi et al. 2009. PubMed ID: 19204907). This variant is reported in 0.0078% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/7-107335062-G-GCAGT). Taken together, this variant is interpreted as pathogenic. |
| Baylor Genetics | RCV003473265 | SCV004201812 | pathogenic | Autosomal recessive nonsyndromic hearing loss 4 | 2024-03-18 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV005031470 | SCV005673629 | pathogenic | Autosomal recessive nonsyndromic hearing loss 4; Pendred syndrome | 2024-04-11 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV001831649 | SCV002079996 | pathogenic | Pendred syndrome | 2020-11-23 | no assertion criteria provided | clinical testing |