Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetics and Molecular Pathology, |
RCV002272786 | SCV002556996 | uncertain significance | Adams-Oliver syndrome 5 | 2020-11-11 | criteria provided, single submitter | clinical testing | The NOTCH1 c.2372A>G missense variant is classified as a VARIANT OF UNCERTAIN SIGNIFICANCE (PM2, PP3) The NOTCH1 c.2372A>G missense variant is a single nucleotide change in exon 15 of the NOTCH1 gene, which is predicted to change the amino acid asparagine at position 791 in the protein to serine. This variant has not been reported in dbSNP and is absent from the population databases (PM2). Whilst this variant has been inherited in this case, there have been reports of different NOTCH1 variants showing reduced penetrance, where apparently unaffected family members carry the same NOTCH1 variant as the proband in those families (PMID: 27077170). This variant has not been reported in the ClinVar or HGMD disease databases. Computational predictions support a deleterious effect on the gene or gene product (PP3). |