Submissions for variant NM_001692.4(ATP6V1B1):c.1155dup (p.Ile386fs)

dbSNP: rs781969081

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000622838	SCV000741040	pathogenic	Inborn genetic diseases	2015-10-23	criteria provided, single submitter	clinical testing
Invitae	RCV000681884	SCV000934190	pathogenic	not provided	2024-01-13	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ile386Hisfs*56) in the ATP6V1B1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATP6V1B1 are known to be pathogenic (PMID: 9916796, 18368028). 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 premature translational stop signal has been observed in individual(s) with renal tubular acidosis with sensorineural deafness (PMID: 9916796, 23923981, 25285676). It is commonly reported in individuals of Tunsian ancestry (PMID: 9916796, 23923981, 25285676). ClinVar contains an entry for this variant (Variation ID: 520772). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity	RCV001271397	SCV003811178	pathogenic	Renal tubular acidosis with progressive nerve deafness	2022-06-17	criteria provided, single submitter	clinical testing
3billion	RCV001271397	SCV004013604	pathogenic	Renal tubular acidosis with progressive nerve deafness		criteria provided, single submitter	clinical testing	The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.003%). The variant is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic without evidence for the classification (ClinVar ID: VCV000520772 / PMID: 9916796). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
GeneDx	RCV000681884	SCV004022570	pathogenic	not provided	2023-07-25	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Considered to be a founder variant in the Tunisian population (Nagara et al., 2014); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34805638, 30586318, 31733597, 24252324, 23923981, 31672324, 28233610, 27140593, 24975934, 9916796, 25285676, 12414817, 31589614)
PreventionGenetics, part of Exact Sciences	RCV003411471	SCV004115016	pathogenic	ATP6V1B1-related condition	2023-06-05	criteria provided, single submitter	clinical testing	The ATP6V1B1 c.1155dupC variant is predicted to result in a frameshift and premature protein termination (p.Ile386Hisfs*56). This variant has been reported to be pathogenic for autosomal recessive renal tubular acidosis with sensorineural deafness (see for example at Cogal et al. 2021. PubMed ID: 34805638; Dahmani et al. 2020. PubMed ID: 31733597). This variant is reported in 0.010% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-71191572-A-AC). Frameshift variants in ATP6V1B1 are expected to be pathogenic. This variant is interpreted as pathogenic.
Gharavi Laboratory, Columbia University	RCV000681884	SCV000809363	pathogenic	not provided	2018-09-16	no assertion criteria provided	research
Natera, Inc.	RCV001271397	SCV001452523	pathogenic	Renal tubular acidosis with progressive nerve deafness	2020-09-16	no assertion criteria provided	clinical testing