Submissions for variant NM_021625.4(TRPV4):c.523A>G (p.Thr175Ala) (rs146304351)

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics Inc	RCV000516838	SCV000615860	uncertain significance	not specified	2017-04-13	criteria provided, single submitter	clinical testing
Invitae	RCV000684901	SCV000812362	uncertain significance	Charcot-Marie-Tooth disease axonal type 2C	2019-10-31	criteria provided, single submitter	clinical testing	This sequence change replaces threonine with alanine at codon 175 of the TRPV4 protein (p.Thr175Ala). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs146304351, ExAC 0.009%). This variant has not been reported in the literature in individuals with TRPV4-related disease. Experimental studies have shown that this missense change disrupts TRPV4 protein function in vitro (PMID: 19661060). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
CeGaT Praxis fuer Humangenetik Tuebingen	RCV000994976	SCV001148823	uncertain significance	not provided	2019-06-01	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV001112861	SCV001270565	uncertain significance	Brachyrachia (short spine dysplasia)	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.
Illumina Clinical Services Laboratory,Illumina	RCV001114213	SCV001272064	uncertain significance	Scapuloperoneal spinal muscular atrophy	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.
Illumina Clinical Services Laboratory,Illumina	RCV001114214	SCV001272065	uncertain significance	Metatrophic dysplasia	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.
Illumina Clinical Services Laboratory,Illumina	RCV000684901	SCV001272066	uncertain significance	Charcot-Marie-Tooth disease axonal type 2C	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.
Illumina Clinical Services Laboratory,Illumina	RCV001114215	SCV001272067	uncertain significance	Distal spinal muscular atrophy, congenital nonprogressive	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.
Illumina Clinical Services Laboratory,Illumina	RCV001114216	SCV001272068	likely benign	Spondylometaphyseal dysplasia, Kozlowski type	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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Molecular Genetics Laboratory,London Health Sciences Centre	RCV001173247	SCV001336330	uncertain significance	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing