Submissions for variant NM_001692.4(ATP6V1B1):c.1349del (p.Gln450fs)

dbSNP: rs1558681020

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001927031	SCV002206457	pathogenic	not provided	2024-02-20	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln450Argfs*37) in the ATP6V1B1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 64 amino acid(s) of the ATP6V1B1 protein. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with ATP6V1B1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1425954). This variant disrupts a region of the ATP6V1B1 protein in which other variant(s) (p.Phe468Cysfs*20) have been determined to be pathogenic (PMID: 8651253, 18368028, 25164082). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV005031907	SCV005659239	likely pathogenic	Renal tubular acidosis with progressive nerve deafness	2024-02-06	criteria provided, single submitter	clinical testing