Submissions for variant NM_007375.4(TARDBP):c.669C>G (p.Pro223=)

gnomAD frequency: 0.00006  dbSNP: rs149517613

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics	RCV000713824	SCV000844461	benign	not provided	2017-12-12	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000713824	SCV001246536	uncertain significance	not provided	2019-11-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001101666	SCV001258293	uncertain significance	Amyotrophic lateral sclerosis type 10	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae	RCV001467552	SCV001671578	likely benign	Amyotrophic lateral sclerosis type 10; TARDBP-related frontotemporal dementia	2024-01-09	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV003303206	SCV003999550	likely benign	Inborn genetic diseases	2023-05-14	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences	RCV003965466	SCV004781096	likely benign	TARDBP-related disorder	2023-03-13	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).