Submissions for variant NM_004380.3(CREBBP):c.2728A>G (p.Thr910Ala)

dbSNP: rs143247685

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000145728	SCV000192848	likely benign	not specified	2014-05-15	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000145728	SCV000202575	benign	not specified	2013-12-18	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000421582	SCV000510827	benign	not provided	2016-09-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002311524	SCV000847072	likely benign	Inborn genetic diseases	2018-04-20	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001087789	SCV001005517	benign	Rubinstein-Taybi syndrome	2024-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000421582	SCV001943541	benign	not provided	2019-04-09	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 20684013)
CeGaT Center for Human Genetics Tuebingen	RCV000421582	SCV002545743	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	CREBBP: BP4, BS1
Breakthrough Genomics, Breakthrough Genomics	RCV000421582	SCV005217368	likely benign	not provided		criteria provided, single submitter	not provided
OMIM	RCV000022942	SCV000044233	pathogenic	Rubinstein-Taybi syndrome due to CREBBP mutations	2010-09-01	no assertion criteria provided	literature only
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille	RCV001252206	SCV001427957	likely benign	Intellectual disability	2019-01-01	no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000145728	SCV001743605	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000421582	SCV001928622	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000145728	SCV001953500	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000421582	SCV001975472	likely benign	not provided		no assertion criteria provided	clinical testing
Practice for Gait Abnormalities, David Pomarino, Competency Network Toe Walking c/o Practice Pomarino	RCV002224958	SCV002503586	likely pathogenic	Tip-toe gait	2022-04-04	no assertion criteria provided	clinical testing	Hereditary motor sensory neuropathy (HMSN), also known as Charcot-Marie-Tooth Disease (CMT), is the most commonly inherited peripheral polyneuropathy. It constitutes a group of inherited, progressive, motor and sensory peripheral nerve disorders with properties of demyelination, axonal degeneration, or both. It is classified by clinical characteristics, modes of inheritance, electrophysiologic features, metabolic defects, and specific gene markers. Our patients all walk on tiptoe, so they show similar symptoms. When we genetically test them with our toe walking panel, we find that around 90 per cent of them have a genetic variant that explains their toe walking. These can be assigned, for example, to the area of myopathies (such as variants of the COL6A3 gene), the area of hereditary neuropathies (such as variants of the KMT2C gene) or the area of metabolic diseases (such as variants of the PYGM gene). In a smaller group of patients with almost identical symptoms, no abnormality is found in the genes of our panel, but spastic paraplegia can be detected. In another small group of our toe walkers, no abnormalities can be detected in the genes analysed in our toe walking panel, nor do they suffer from spastic paraplegia, as is also the case with healthy children. In contrast to these, however, they show a tiptoe gait. These patients suffer from infantile cerebral palsy, in which toe walking can also be observed.
PreventionGenetics, part of Exact Sciences	RCV003974853	SCV004797551	benign	CREBBP-related disorder	2019-04-15	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).