Submissions for variant NM_000531.6(OTC):c.944T>A (p.Val315Asp)

dbSNP: rs67414444

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000690668	SCV000818367	pathogenic	Ornithine carbamoyltransferase deficiency	2018-06-13	criteria provided, single submitter	clinical testing	This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. Other different missense substitutions at this codon (p.Val315Gly, p.Val315Phe) have been reported in the literature in individuals affected with OTC deficieny (PMID: 10946359, 16786505). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been reported in an individual affected with OTC deficiency (PMID: 10946359). Additionally, this variant has been observed to be de novo in an individual affected with OTC deficiency (Invitae). ClinVar contains an entry for this variant (Variation ID: 97366). This sequence change replaces valine with aspartic acid at codon 315 of the OTC protein (p.Val315Asp). The valine residue is highly conserved and there is a large physicochemical difference between valine and aspartic acid.
CeGaT Center for Human Genetics Tuebingen	RCV000083615	SCV001249296	pathogenic	not provided	2019-07-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000690668	SCV002033231	pathogenic	Ornithine carbamoyltransferase deficiency	2021-11-07	criteria provided, single submitter	clinical testing
GenMed Metabolism Lab	RCV000083615	SCV000115701	pathogenic	not provided		no assertion criteria provided	not provided	Converted during submission to Pathogenic.