Submissions for variant NM_020458.4(TTC7A):c.2312C>T (p.Ala771Val)

gnomAD frequency: 0.00001  dbSNP: rs538380438

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001361574	SCV001557552	uncertain significance	Multiple gastrointestinal atresias	2021-08-31	criteria provided, single submitter	clinical testing	This sequence change replaces alanine with valine at codon 771 of the TTC7A protein (p.Ala771Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs538380438, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with TTC7A-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528365	SCV001740012	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001528365	SCV001965471	uncertain significance	not provided		no assertion criteria provided	clinical testing