Submissions for variant NM_001904.4(CTNNB1):c.1494dup (p.His499fs)

dbSNP: rs1553631896

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000627529	SCV000705263	pathogenic	not provided	2017-04-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000627529	SCV000748529	pathogenic	not provided	2018-04-04	criteria provided, single submitter	clinical testing	The c.1494dupA variant in the CTNNB1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.1494dupA variant causes a frameshift starting with codon Histidine 499, changes this amino acid to aThreonine residue, and creates a premature Stop codon at position 31 of the new reading frame, denoted p.His499ThrfsX31. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1494dupA variant is not observed in large population cohorts (Lek et al., 2016).
Mendelics	RCV000987260	SCV001136510	pathogenic	Hepatocellular carcinoma	2019-05-28	criteria provided, single submitter	clinical testing
Invitae	RCV000627529	SCV002236521	pathogenic	not provided	2022-11-01	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: 499655). This premature translational stop signal has been observed in individual(s) with clinical features of CTNNB1-related conditions (PMID: 29682453). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.His499Thrfs*31) in the CTNNB1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CTNNB1 are known to be pathogenic (PMID: 23033978, 24614104, 25326669, 26350204, 28575650).