Submissions for variant NM_024665.7(TBL1XR1):c.343G>A (p.Ala115Thr)

gnomAD frequency: 0.00022  dbSNP: rs375411293

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000768329	SCV000899009	uncertain significance	Pierpont syndrome; Intellectual disability, autosomal dominant 41		criteria provided, single submitter	clinical testing	TBL1XR1 NM_024665.5 exon 5 p.Ala115Thr (c.343G>A): This variant has not been reported in the literature but is present in 34/125618 European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs375411293). This variant amino acid Threonine (Thr) is present in 7 species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000809213	SCV000949356	likely benign	Pierpont syndrome	2025-01-06	criteria provided, single submitter	clinical testing
GeneDx	RCV001692285	SCV001915186	benign	not provided	2019-04-05	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002458375	SCV002617113	likely benign	Inborn genetic diseases	2024-02-06	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.
CeGaT Center for Human Genetics Tuebingen	RCV001692285	SCV004149429	likely benign	not provided	2025-03-01	criteria provided, single submitter	clinical testing	TBL1XR1: PP2, BP4, BS2
PreventionGenetics, part of Exact Sciences	RCV004549838	SCV004759896	likely benign	TBL1XR1-related disorder	2023-07-28	no assertion criteria provided	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).