Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000669625 | SCV001323032 | 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, |
RCV001004635 | SCV001323033 | 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). 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. |
Genome- |
RCV001004635 | SCV001806725 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 4 | 2021-07-22 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV000669625 | SCV001806726 | uncertain significance | Pendred syndrome | 2021-07-22 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV000669625 | SCV002060311 | uncertain significance | Pendred syndrome | 2021-11-09 | criteria provided, single submitter | clinical testing | NM_000441.1(SLC26A4):c.1195T>C(S399P) is a missense variant classified as a variant of uncertain significance in the context of Pendred syndrome. S399P has been observed in a case with relevant disease (PMID: 16283880). Functional assessments of this variant are available in the literature (PMID: 31599023). S399P has been observed in population frequency databases (gnomAD: SAS 0.09%). In summary, there is insufficient evidence to classify NM_000441.1(SLC26A4):c.1195T>C(S399P) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening. |
Fulgent Genetics, |
RCV002499166 | SCV002784222 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 4; Pendred syndrome | 2022-02-28 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002531233 | SCV003519622 | uncertain significance | not provided | 2022-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 399 of the SLC26A4 protein (p.Ser399Pro). This variant is present in population databases (rs747431002, gnomAD 0.09%). This missense change has been observed in individual(s) with non-syndromic deafness (PMID: 16283880). ClinVar contains an entry for this variant (Variation ID: 554065). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SLC26A4 protein function. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on SLC26A4 function (PMID: 31599023). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Gene |
RCV002531233 | SCV003921568 | uncertain significance | not provided | 2023-03-21 | criteria provided, single submitter | clinical testing | Identified in the heterozygous state in individuals with nonsyndromic hearing loss, and no second SLC26A4 variant was identified (Hutchin et al., 2005; Adhikary et al., 2015); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Published functional studies demonstrate impaired I-/Cl- antiport activities, but no effect on the HCO3-/Cl- antiport activities (Wasano et al., 2020); This variant is associated with the following publications: (PMID: 34426522, 26188157, 33199029, 35186384, 31599023, 16283880, 27771369) |
National Institute of Sensory Organs, |
RCV001004635 | SCV000994883 | affects | Autosomal recessive nonsyndromic hearing loss 4 | 2019-08-20 | no assertion criteria provided | literature only | in vitro experiment |