TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24624	74095;74096;74097	chr2:178572262;178572261;178572260	chr2:179436989;179436988;179436987
N2AB	22983	69172;69173;69174	chr2:178572262;178572261;178572260	chr2:179436989;179436988;179436987
N2A	22056	66391;66392;66393	chr2:178572262;178572261;178572260	chr2:179436989;179436988;179436987
N2B	15559	46900;46901;46902	chr2:178572262;178572261;178572260	chr2:179436989;179436988;179436987
Novex-1	15684	47275;47276;47277	chr2:178572262;178572261;178572260	chr2:179436989;179436988;179436987
Novex-2	15751	47476;47477;47478	chr2:178572262;178572261;178572260	chr2:179436989;179436988;179436987
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-67
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.3059
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
T/I	None	None	0.998	N	0.806	0.43	0.560153176789	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
T/A	0.1102	likely_benign	0.1038	benign	-0.733	Destabilizing	0.514	D	0.471	neutral	N	0.518905663	None	None	N
T/C	0.4129	ambiguous	0.4266	ambiguous	-0.494	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
T/D	0.6128	likely_pathogenic	0.5894	pathogenic	0.215	Stabilizing	0.987	D	0.745	deleterious	None	None	None	None	N
T/E	0.5265	ambiguous	0.4858	ambiguous	0.259	Stabilizing	0.996	D	0.747	deleterious	None	None	None	None	N
T/F	0.2705	likely_benign	0.2253	benign	-0.808	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
T/G	0.314	likely_benign	0.3115	benign	-1.015	Destabilizing	0.994	D	0.644	neutral	None	None	None	None	N
T/H	0.2868	likely_benign	0.2828	benign	-1.196	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
T/I	0.158	likely_benign	0.1344	benign	-0.069	Destabilizing	0.998	D	0.806	deleterious	N	0.518348303	None	None	N
T/K	0.3607	ambiguous	0.3524	ambiguous	-0.432	Destabilizing	0.997	D	0.749	deleterious	None	None	None	None	N
T/L	0.1096	likely_benign	0.0971	benign	-0.069	Destabilizing	0.995	D	0.625	neutral	None	None	None	None	N
T/M	0.0949	likely_benign	0.0861	benign	-0.045	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
T/N	0.1495	likely_benign	0.1507	benign	-0.553	Destabilizing	0.982	D	0.625	neutral	N	0.51028618	None	None	N
T/P	0.6895	likely_pathogenic	0.696	pathogenic	-0.257	Destabilizing	0.991	D	0.809	deleterious	N	0.51556992	None	None	N
T/Q	0.3038	likely_benign	0.2958	benign	-0.558	Destabilizing	0.997	D	0.817	deleterious	None	None	None	None	N
T/R	0.3005	likely_benign	0.2892	benign	-0.351	Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
T/S	0.1172	likely_benign	0.1133	benign	-0.881	Destabilizing	0.166	N	0.225	neutral	N	0.487483891	None	None	N
T/V	0.1268	likely_benign	0.1111	benign	-0.257	Destabilizing	0.993	D	0.524	neutral	None	None	None	None	N
T/W	0.7124	likely_pathogenic	0.6882	pathogenic	-0.798	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
T/Y	0.3421	ambiguous	0.3193	benign	-0.508	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.