Submissions for variant NM_004064.5(CDKN1B):c.31C>T (p.Pro11Ser)

gnomAD frequency: 0.00004  dbSNP: rs779193240

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000466839	SCV000541765	uncertain significance	Multiple endocrine neoplasia type 4	2024-02-01	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 11 of the CDKN1B protein (p.Pro11Ser). This variant is present in population databases (rs779193240, gnomAD 0.007%). This missense change has been observed in individual(s) with prostate cancer (PMID: 17372254). ClinVar contains an entry for this variant (Variation ID: 404268). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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	RCV000567002	SCV000673205	likely benign	Hereditary cancer-predisposing syndrome	2023-01-05	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx	RCV003128801	SCV003805808	uncertain significance	not provided	2022-08-26	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in an individual with prostate cancer (Cybulski et al., 2007); This variant is associated with the following publications: (PMID: 17372254)
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University	RCV003153576	SCV003843619	likely pathogenic	Ovarian cancer	2022-01-01	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000466839	SCV005060218	uncertain significance	Multiple endocrine neoplasia type 4	2024-02-06	criteria provided, single submitter	clinical testing
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas	RCV000466839	SCV004041657	uncertain significance	Multiple endocrine neoplasia type 4	2023-10-09	no assertion criteria provided	clinical testing