Submissions for variant NM_205836.3(FBXO38):c.51T>G (p.Ile17Met)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV005104895	SCV005819866	uncertain significance	Distal hereditary motor neuropathy type 2	2024-03-28	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 17 of the FBXO38 protein (p.Ile17Met). This variant is present in population databases (rs751405536, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with FBXO38-related conditions. 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 FBXO38 protein function with a negative 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.
PreventionGenetics, part of Exact Sciences	RCV004757068	SCV005365783	uncertain significance	FBXO38-related disorder	2024-05-06	no assertion criteria provided	clinical testing	The FBXO38 c.51T>G variant is predicted to result in the amino acid substitution p.Ile17Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0031% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/5-147774390-T-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.