Submissions for variant NM_002055.5(GFAP):c.734T>C (p.Met245Thr)

gnomAD frequency: 0.00003  dbSNP: rs151327900

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002011757	SCV002298897	uncertain significance	not provided	2024-04-23	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 245 of the GFAP protein (p.Met245Thr). This variant is present in population databases (rs151327900, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with GFAP-related conditions. ClinVar contains an entry for this variant (Variation ID: 1510421). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GFAP protein function. 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.
CeGaT Center for Human Genetics Tuebingen	RCV002011757	SCV004009808	likely benign	not provided	2023-04-01	criteria provided, single submitter	clinical testing	GFAP: BS2