Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000733343 | SCV000861396 | uncertain significance | not provided | 2018-05-22 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001868985 | SCV002174932 | uncertain significance | Hajdu-Cheney syndrome | 2022-07-26 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1726 of the NOTCH2 protein (p.Arg1726His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with NOTCH2-related conditions (PMID: 32368696). ClinVar contains an entry for this variant (Variation ID: 597278). 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: "Tolerated"; 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. |
Prevention |
RCV003396310 | SCV004105892 | uncertain significance | NOTCH2-related condition | 2023-09-03 | criteria provided, single submitter | clinical testing | The NOTCH2 c.5177G>A variant is predicted to result in the amino acid substitution p.Arg1726His. This variant was reported de novo in at least one individual with congenital heart defects (Patient #1-06209 in supplementary databases 1 and 2, Edwards et al. 2020. PubMed ID: 32368696; Table S2, Sevim Bayrak et al. 2020. PubMed ID: 31941532). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |