Submissions for variant NM_004380.3(CREBBP):c.5837del (p.Pro1946fs)

dbSNP: rs587783507

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000145772	SCV000192900	pathogenic	Rubinstein-Taybi syndrome due to CREBBP mutations	2013-02-08	criteria provided, single submitter	clinical testing
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	RCV000681911	SCV002051535	likely pathogenic	not provided	2020-12-28	criteria provided, single submitter	clinical testing	PVS1, PS4_Moderate
Labcorp Genetics (formerly Invitae), Labcorp	RCV005089680	SCV005838461	pathogenic	Rubinstein-Taybi syndrome	2024-05-22	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Pro1946Hisfs*30) in the CREBBP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 497 amino acid(s) of the CREBBP protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with clinical features of CREBBP-related conditions and/or Rubinstein-Taybi syndrome (PMID: 25388907, 30586318, 31637876; Invitae). ClinVar contains an entry for this variant (Variation ID: 158391). This variant disrupts a region of the CREBBP protein in which other variant(s) (p.Arg2004*) have been determined to be pathogenic (PMID: 15706485, 21932317). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Gharavi Laboratory, Columbia University	RCV000681911	SCV000809394	likely pathogenic	not provided	2018-09-16	no assertion criteria provided	research