Submissions for variant NM_172362.3(KCNH1):c.2162T>C (p.Met721Thr)

gnomAD frequency: 0.00008  dbSNP: rs140043333

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV002132119	SCV002403202	benign	not provided	2023-11-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV003025435	SCV003719342	likely benign	Inborn genetic diseases	2022-12-13	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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003224614	SCV003920091	uncertain significance	Zimmermann-Laband syndrome 1; Temple-Baraitser syndrome	2022-07-22	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF 0.02% (17/68020) (https://gnomad.broadinstitute.org/variant/1-210684089-A-G?dataset=gnomad_r3). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
CeGaT Center for Human Genetics Tuebingen	RCV002132119	SCV004125541	likely benign	not provided	2023-08-01	criteria provided, single submitter	clinical testing	KCNH1: PP2, BS2