Submissions for variant NM_001371986.1(UNC80):c.1078C>T (p.Arg360Ter)

gnomAD frequency: 0.00001  dbSNP: rs200659479

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Department Of Translational Genomics (developmental Genetics Section), King Faisal Specialist Hospital & Research Centre	RCV000203562	SCV000258547	likely pathogenic	Encephalopathy	2015-09-01	criteria provided, single submitter	research
Revvity Omics, Revvity	RCV000207471	SCV002020819	pathogenic	Hypotonia, infantile, with psychomotor retardation and characteristic facies 2	2019-06-21	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004528993	SCV004110661	pathogenic	UNC80-related disorder	2023-02-13	criteria provided, single submitter	clinical testing	The UNC80 c.1078C>T variant is predicted to result in premature protein termination (p.Arg360*). This variant was reported in the homozygous state to be causative for autosomal recessive infantile encephalopathy (Shamseldin et al. 2016. PubMed ID: 26708753; Supplementary material, Alfares et al. 2017. PubMed ID: 28454995). This variant is reported in 0.011% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-210678443-C-T). Nonsense variants in UNC80 are expected to be pathogenic. This variant is interpreted as pathogenic.
Invitae	RCV003556261	SCV004293061	pathogenic	not provided	2023-01-26	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 219189). This premature translational stop signal has been observed in individual(s) with UNC80-related conditions (PMID: 26708753). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Arg360*) in the UNC80 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in UNC80 are known to be pathogenic (PMID: 26545877, 26708751, 26708753).
OMIM	RCV000207471	SCV000262743	pathogenic	Hypotonia, infantile, with psychomotor retardation and characteristic facies 2	2016-01-07	no assertion criteria provided	literature only
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	RCV000207471	SCV001133095	likely pathogenic	Hypotonia, infantile, with psychomotor retardation and characteristic facies 2	2019-09-26	no assertion criteria provided	clinical testing