ClinGen Dosage Sensitivity Curation Page


Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function phenotype
PubMed ID Description
25505254 Aoude et al. (2015) screened individuals with cutaneous malignant melanoma who previously tested negative for CDKN2A, BAP1, POT1, BRCA2, CDK4, and TERT promoter pathogenic variation as well as a control cohort for germline variation in shelterin genes. ACD p.Q320X (NM_001082486 c.958C>T) was identified in one family and observed in all four affected individuals available for testing. This nonsense variation occurs in POT1 binding domain, which seems to be enriched for missense mutation in the CMM cohort, and is not in the penultimate nor final exon.

Evidence for Triplosenstive Phenotype

NOTE:The loss of function score should be used to evaluate deletions, and the triplosensitivity score should be used to evaluated duplications. CNVs encompassing more than one gene must be evaluated in their totality (e.g. overall size, gain vs. loss, presence of other genes, etc). The rating of a single gene within the CNV should not necessarily be the only criteria by which one defines a clinical interpretation. Individual interpretations must take into account the phenotype described for the patient as well as issues of penetrance and expressivity of the disorder. ACMG has published guidelines for the characterization of postnatal CNVs, and these recommendations should be utilized (Genet Med (2011)13: 680-685). Exceptions to these interpretive correlations will occur, and clinical judgment should always be exercised.