Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001062827 | SCV001227650 | uncertain significance | Multiple endocrine neoplasia type 4 | 2019-04-10 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CDKN1B-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with tyrosine at codon 129 of the CDKN1B protein (p.His129Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. |
Ambry Genetics | RCV003307899 | SCV004004486 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-03 | criteria provided, single submitter | clinical testing | The p.H129Y variant (also known as c.385C>T), located in coding exon 1 of the CDKN1B gene, results from a C to T substitution at nucleotide position 385. The histidine at codon 129 is replaced by tyrosine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |