Submissions for variant NM_003865.3(HESX1):c.313T>G (p.Trp105Gly)

gnomAD frequency: 0.00001  dbSNP: rs754137696

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001298588	SCV001487649	uncertain significance	Septo-optic dysplasia sequence; GROWTH HORMONE DEFICIENCY WITH PITUITARY ANOMALIES	2023-09-17	criteria provided, single submitter	clinical testing	This sequence change replaces tryptophan, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 105 of the HESX1 protein (p.Trp105Gly). This variant is present in population databases (rs754137696, gnomAD 0.1%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with HESX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 492850). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Mendelics	RCV002248803	SCV002517177	uncertain significance	not specified	2022-05-04	criteria provided, single submitter	clinical testing
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000583407	SCV000692277	pathogenic	Septo-optic dysplasia sequence	2008-06-03	no assertion criteria provided	clinical testing
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000581469	SCV000692278	pathogenic	Pituitary hormone deficiency, combined, 1	2008-06-03	no assertion criteria provided	clinical testing