Submissions for variant NM_004260.4(RECQL4):c.2312C>T (p.Thr771Met)

gnomAD frequency: 0.00001  dbSNP: rs770327474

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000634287	SCV000755590	uncertain significance	Baller-Gerold syndrome	2023-12-30	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 771 of the RECQL4 protein (p.Thr771Met). This variant is present in population databases (rs770327474, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with RECQL4-related conditions. This missense change has been observed to be homozygous or hemizygous in an individual who did not have the expected clinical features for that genetic result (Invitae). ClinVar contains an entry for this variant (Variation ID: 528990). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RECQL4 protein function with a positive predictive value of 80%. 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.
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University	RCV003153778	SCV003843696	likely pathogenic	Ovarian cancer	2022-01-01	criteria provided, single submitter	clinical testing