Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001244095 | SCV001417293 | uncertain significance | Nephronophthisis | 2022-07-26 | 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 680 of the NPHP4 protein (p.Thr680Met). This variant is present in population databases (rs370238544, gnomAD 0.03%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with NPHP4-related conditions. ClinVar contains an entry for this variant (Variation ID: 968861). 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: "Probably 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. |
Ambry Genetics | RCV002564083 | SCV003543269 | uncertain significance | Inborn genetic diseases | 2021-12-07 | criteria provided, single submitter | clinical testing | The c.2039C>T (p.T680M) alteration is located in exon 16 (coding exon 15) of the NPHP4 gene. This alteration results from a C to T substitution at nucleotide position 2039, causing the threonine (T) at amino acid position 680 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Prevention |
RCV003414058 | SCV004116865 | uncertain significance | NPHP4-related condition | 2023-03-02 | criteria provided, single submitter | clinical testing | The NPHP4 c.2039C>T variant is predicted to result in the amino acid substitution p.Thr680Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.028% of alleles in individuals of European (Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-5964781-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |