ClinVar Miner

Submissions for variant NM_005993.5(TBCD):c.2280C>A (p.Tyr760Ter)

dbSNP: rs754750539
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523090 SCV000618451 pathogenic not provided 2017-07-18 criteria provided, single submitter clinical testing The Y760X variant in the TBCD gene has been reported previously in the compound heterozygous state with a second TBCD variant in association with early-onset neurodegenerative encephalopathy (Miyake et al., 2016). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Y760X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret Y760X as a pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV000523090 SCV004296899 pathogenic not provided 2023-06-20 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: 268170). This premature translational stop signal has been observed in individual(s) with early-onset neurodegenerative encephalopathy (PMID: 27666374). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr760*) in the TBCD gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TBCD are known to be pathogenic (PMID: 27666370, 27666374).
OMIM RCV000258906 SCV000328659 pathogenic Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome 2016-11-16 no assertion criteria provided literature only

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