Submissions for variant NM_006087.4(TUBB4A):c.523G>A (p.Val175Met)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV003314961	SCV004014406	likely pathogenic	not provided	2025-01-08	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003388221	SCV004099712	uncertain significance	not specified	2023-09-11	criteria provided, single submitter	clinical testing	Variant summary: TUBB4A c.523G>A (p.Val175Met) results in a conservative amino acid change located in the Tubulin/FtsZ, GTPase domain (IPR003008) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251490 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. At least one de novo occurrence of c.523G>A in an individual affected with cerebellar ataxia, hypotonia, global developmental delay, and cognitive impairment has been seen in our lab. To our knowledge, no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter has assessed the variant since 2014, and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.