Submissions for variant NM_003412.4(ZIC1):c.512T>C (p.Met171Thr)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003731192	SCV004529738	uncertain significance	not provided	2023-08-22	criteria provided, single submitter	clinical testing	This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 171 of the ZIC1 protein (p.Met171Thr). 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. 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 not expected to disrupt ZIC1 protein function. This variant has not been reported in the literature in individuals affected with ZIC1-related conditions. This variant is present in population databases (rs751258379, gnomAD 0.006%).
Ambry Genetics	RCV004374167	SCV004983955	uncertain significance	Inborn genetic diseases	2024-02-27	criteria provided, single submitter	clinical testing	The c.512T>C (p.M171T) alteration is located in exon 1 (coding exon 1) of the ZIC1 gene. This alteration results from a T to C substitution at nucleotide position 512, causing the methionine (M) at amino acid position 171 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.