Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001039515 | SCV001203047 | uncertain significance | not provided | 2022-04-18 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 440 of the CLCN4 protein (p.Thr440Met). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CLCN4-related conditions. ClinVar contains an entry for this variant (Variation ID: 838049). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 |
RCV001039515 | SCV001774136 | likely benign | not provided | 2018-12-06 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV001039515 | SCV005411408 | uncertain significance | not provided | 2023-07-06 | criteria provided, single submitter | clinical testing | BS2, PP2 |
Ambry Genetics | RCV004973264 | SCV005554197 | uncertain significance | Inborn genetic diseases | 2024-09-30 | criteria provided, single submitter | clinical testing | The c.1319C>T (p.T440M) alteration is located in exon 9 (coding exon 7) of the CLCN4 gene. This alteration results from a C to T substitution at nucleotide position 1319, causing the threonine (T) at amino acid position 440 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |