Submissions for variant NM_001199107.2(TBC1D24):c.951C>T (p.Thr317=)

gnomAD frequency: 0.00003  dbSNP: rs766745103

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000189673	SCV000243319	benign	not specified	2014-10-14	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000189673	SCV000270894	likely benign	not specified	2017-08-10	criteria provided, single submitter	clinical testing	p.Thr317Thr in exon 2 of TBC1D24: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 13/265438 total chromosomes in different populations by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs766745103).
Illumina Laboratory Services, Illumina	RCV000397672	SCV000396210	uncertain significance	Familial infantile myoclonic epilepsy	2018-01-12	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	RCV000651581	SCV000773435	likely benign	Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24	2023-10-28	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002317659	SCV000850063	likely benign	Inborn genetic diseases	2017-11-02	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
CeGaT Center for Human Genetics Tuebingen	RCV001815242	SCV002063474	likely benign	not provided	2021-12-01	criteria provided, single submitter	clinical testing