Submissions for variant NM_001083962.2(TCF4):c.1849G>T (p.Val617Phe)

dbSNP: rs1568303086

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678346	SCV000804410	likely pathogenic	Pitt-Hopkins syndrome	2017-03-29	criteria provided, single submitter	provider interpretation	This 6 year old male with global developmental delays, hypotonia, cryptorchidism, and large stature was found to carry a missense variant in the TCF4 gene. At the date of report, he had no history of seizure activity or hypervenitlation, but he was noted to have dysmorphic features, including mild brachycephaly, narrow palpebral fissures, overfolded helices and small, pointed tragi, a single transverse palmar crease on the right hand, and a shortened transverse palmar crease on the left hand. The p.Val617Phe variant is absent from population databases and has not been reported in other individuals with Pitt-Hopkins syndrome, to our knowledge. Computational models predict the variant to be probably damaging. A variant at codon 614 has been reported previously in an individual with Pitt-Hopkins, which supports the functional importance of this region.
MGZ Medical Genetics Center	RCV000678346	SCV002579827	likely pathogenic	Pitt-Hopkins syndrome	2022-02-17	criteria provided, single submitter	clinical testing