Submissions for variant NM_018196.4(TMLHE):c.229C>T (p.Arg77Ter)

gnomAD frequency: 0.00005  dbSNP: rs781889971

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000256080	SCV000322111	uncertain significance	not provided	2018-10-23	criteria provided, single submitter	clinical testing	The R77X variant in the TMLHE gene has been reported previously in two male siblings with autism and moderate intellectual disability who had elevated 6-N-trimethyllysine, the TMLHE substrate; however, these individuals harbored additional variants in other x-linked genes that may also have contributed to the autism and intellectual disability (Nava et al., 2012). This variant may cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R77X variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret R77X as a variant of uncertain significance.
Diagnostic Laboratory, Strasbourg University Hospital	RCV001260784	SCV001437876	uncertain significance	Intellectual disability	2020-09-10	criteria provided, single submitter	clinical testing
OMIM	RCV000210875	SCV000267175	risk factor	Epsilon-trimethyllysine hydroxylase deficiency	2012-10-23	no assertion criteria provided	literature only