Submissions for variant NM_006087.4(TUBB4A):c.1162A>G (p.Met388Val)

dbSNP: rs886041019

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000433083	SCV000521222	likely pathogenic	not provided	2017-01-23	criteria provided, single submitter	clinical testing	The M388V variant in the TUBB4A gene has been reported previously in association with hypomyelinating leukodystrophy with atrophy of the basal ganglia and cerebellum (Hamilton et al., 2014; Miyatake et al., 2014). The M388V variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The M388V variant is a conservative amino acid substitution, which occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Missense variants in the same residue (M388I, M388T) have also been reported in association with hypomyelinating leukodystrophy with atrophy of the basal ganglia and cerebellum (Hamilton et al., 2014; Posey et al., 2016), supporting the functional importance of this region of the protein. The M388V variant is a strong candidate for a pathogenic variant.
Revvity Omics, Revvity	RCV000433083	SCV002021564	likely pathogenic	not provided	2019-09-20	criteria provided, single submitter	clinical testing
GeneReviews	RCV000258588	SCV000328478	not provided	Hypomyelinating leukodystrophy 6		no assertion provided	literature only