Submissions for variant NM_013444.4(UBQLN2):c.1019G>T (p.Ser340Ile)

gnomAD frequency: 0.00002  dbSNP: rs201549050

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002162796	SCV002416950	likely benign	Amyotrophic lateral sclerosis type 15	2024-10-18	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003403700	SCV004121211	uncertain significance	UBQLN2-related disorder	2023-05-26	criteria provided, single submitter	clinical testing	The UBQLN2 c.1019G>T variant is predicted to result in the amino acid substitution p.Ser340Ile. This variant was reported in an individual with amyotrophic lateral sclerosis (ALS) (McCann et al. 2020. PubMed ID: 32409511). This variant was also reported in a female individual (63 yr) and her affected sister with ALS; however, this variant was also identified in the proband's unaffected elder brother. The author suggested incomplete penetrance in this family (Kotan et al. 2016. PubMed ID: 28373810). This variant is reported in 0.0037% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/X-56591325-G-T) and is interpreted as likely benign in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/1607950/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
CeGaT Center for Human Genetics Tuebingen	RCV003883774	SCV004699497	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	UBQLN2: BP4