Submissions for variant NM_001173990.3(TMEM216):c.211G>T (p.Val71Leu)

gnomAD frequency: 0.00251  dbSNP: rs57932685

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000177125	SCV000228952	benign	not specified	2015-01-14	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000177125	SCV000306944	likely benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV000177125	SCV000536311	uncertain significance	not specified	2017-01-24	criteria provided, single submitter	clinical testing	The V71L variant has been previously reported as a benign polymorphism which showed stable expression of the protein similar to wild type expression (Valente et al., 2010). This variant is observed in 70/9798 (0.7%) alleles from individuals of African background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The V71L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Valine are tolerated across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Additionally, missense variants in a nearby residue (R73C/H/L) have been reported in Human Gene Mutation Database in association with Joubert syndrome (Stenson et al., 2014). Based on the currently available information, it is unclear whether the V71L variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000533045	SCV000634558	likely benign	Familial aplasia of the vermis	2025-01-23	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001279272	SCV001466355	likely benign	Joubert syndrome 2	2020-07-17	no assertion criteria provided	clinical testing