Submissions for variant NM_000166.6(GJB1):c.705C>A (p.Phe235Leu)

dbSNP: rs760150310

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Baylor Genetics	RCV001329668	SCV001521170	uncertain significance	Charcot-Marie-Tooth disease X-linked dominant 1	2020-04-14	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003235550	SCV003934332	uncertain significance	not specified	2023-05-16	criteria provided, single submitter	clinical testing	Variant summary: GJB1 c.705C>A (p.Phe235Leu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 176950 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.705C>A in individuals affected with Charcot-Marie-Tooth disease X-linked dominant 1 and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified it as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.