Submissions for variant NM_004304.5(ALK):c.781C>T (p.Arg261Ter)

dbSNP: rs972790555

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000550182	SCV000648774	uncertain significance	Neuroblastoma, susceptibility to, 3	2024-10-16	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg261*) in the ALK gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in ALK cause disease. 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 variant has not been reported in the literature in individuals affected with ALK-related conditions. ClinVar contains an entry for this variant (Variation ID: 470900). 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.
PreventionGenetics, part of Exact Sciences	RCV003409805	SCV004115841	uncertain significance	ALK-related disorder	2022-09-29	criteria provided, single submitter	clinical testing	The ALK c.781C>T variant is predicted to result in premature protein termination (p.Arg261*). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-29940450-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.