Submissions for variant NM_016156.5(MTMR2):c.1855T>C (p.Ser619Pro) (rs116750638)

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001084287	SCV000290180	benign	Charcot-Marie-Tooth disease type 4	2019-12-31	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000219297	SCV000614130	benign	not provided	2019-04-10	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV001112850	SCV001270554	uncertain significance	Charcot-Marie-Tooth disease, type 4B1	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Molecular Genetics Laboratory,London Health Sciences Centre	RCV001172718	SCV001335784	likely benign	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
GeneDx	RCV000219297	SCV000279113	not provided	not provided	2016-07-15	no assertion provided	clinical testing	The S619P variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The NHLBI Exome Sequencing Project reports S619P was observed in 21/8596 (0.2%) alleles from individuals of European background. The 1000 Genomes Project reports S619P was observed in 17/978 (1.7%) alleles from individuals of South Asian background and in 6/206 (3.0%) alleles from individuals of Gujarati Indian background, indicating it may be a rare (benign) variant in these populations. The S619P variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.