Submissions for variant NM_001083962.2(TCF4):c.514_517del (p.Lys172fs)

dbSNP: rs398123561

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000255366	SCV000111340	pathogenic	not provided	2016-06-28	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Strasbourg University Hospital	RCV000224701	SCV000281728	pathogenic	Intellectual disability	2014-07-25	criteria provided, single submitter	clinical testing
GeneDx	RCV000255366	SCV000322052	pathogenic	not provided	2022-08-28	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 22045651, 25167861, 31105003, 32959227, 26147798, 28569743, 25780760, 22722829, 31785789, 22460224)
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV000995665	SCV001149961	pathogenic	Pitt-Hopkins syndrome	2019-05-15	criteria provided, single submitter	clinical testing
Clinical Genetics and Genomics, Karolinska University Hospital	RCV000255366	SCV001449866	pathogenic	not provided	2016-06-30	criteria provided, single submitter	clinical testing
Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes	RCV001374933	SCV001572221	pathogenic	Neurodevelopmental disorder	2020-02-21	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000255366	SCV001746548	pathogenic	not provided	2021-06-01	criteria provided, single submitter	clinical testing
Centogene AG - the Rare Disease Company	RCV000995665	SCV002059376	pathogenic	Pitt-Hopkins syndrome	2019-02-11	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000995665	SCV004297853	pathogenic	Pitt-Hopkins syndrome	2023-07-12	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Lys172Phefs*61) in the TCF4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TCF4 are known to be pathogenic (PMID: 18728071, 22045651). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 93545). This premature translational stop signal has been observed in individual(s) with Pitt-Hopkins syndrome (PMID: 22045651). This variant is not present in population databases (gnomAD no frequency).