TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23487	70684;70685;70686	chr2:178575673;178575672;178575671	chr2:179440400;179440399;179440398
N2AB	21846	65761;65762;65763	chr2:178575673;178575672;178575671	chr2:179440400;179440399;179440398
N2A	20919	62980;62981;62982	chr2:178575673;178575672;178575671	chr2:179440400;179440399;179440398
N2B	14422	43489;43490;43491	chr2:178575673;178575672;178575671	chr2:179440400;179440399;179440398
Novex-1	14547	43864;43865;43866	chr2:178575673;178575672;178575671	chr2:179440400;179440399;179440398
Novex-2	14614	44065;44066;44067	chr2:178575673;178575672;178575671	chr2:179440400;179440399;179440398
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: Fn3-58
• Domain position: 53
• Structural Position: 70
• Q(SASA): 0.4918
• 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	0.983	N	0.76	0.355	0.39162414616	gnomAD-4.0.0	2.73715E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69865E-06	1.15947E-05	0
T/S	None	None	0.008	N	0.307	0.124	0.124217242631	gnomAD-4.0.0	6.84287E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99549E-07	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	0.0983	likely_benign	0.0834	benign	-0.675	Destabilizing	0.106	N	0.453	neutral	N	0.482923433	None	None	N
T/C	0.6407	likely_pathogenic	0.5436	ambiguous	-0.342	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
T/D	0.601	likely_pathogenic	0.5225	ambiguous	-0.131	Destabilizing	0.892	D	0.689	prob.neutral	None	None	None	None	N
T/E	0.5342	ambiguous	0.4707	ambiguous	-0.186	Destabilizing	0.965	D	0.688	prob.neutral	None	None	None	None	N
T/F	0.5267	ambiguous	0.4343	ambiguous	-0.986	Destabilizing	0.995	D	0.785	deleterious	None	None	None	None	N
T/G	0.2847	likely_benign	0.2107	benign	-0.857	Destabilizing	0.908	D	0.623	neutral	None	None	None	None	N
T/H	0.4898	ambiguous	0.4048	ambiguous	-1.203	Destabilizing	0.999	D	0.75	deleterious	None	None	None	None	N
T/I	0.383	ambiguous	0.3334	benign	-0.296	Destabilizing	0.983	D	0.76	deleterious	N	0.468162326	None	None	N
T/K	0.4846	ambiguous	0.4432	ambiguous	-0.597	Destabilizing	0.975	D	0.693	prob.neutral	None	None	None	None	N
T/L	0.1581	likely_benign	0.1299	benign	-0.296	Destabilizing	0.917	D	0.622	neutral	None	None	None	None	N
T/M	0.1342	likely_benign	0.1233	benign	0.091	Stabilizing	0.999	D	0.742	deleterious	None	None	None	None	N
T/N	0.1882	likely_benign	0.1465	benign	-0.374	Destabilizing	0.862	D	0.678	prob.neutral	N	0.486387813	None	None	N
T/P	0.1747	likely_benign	0.135	benign	-0.392	Destabilizing	0.927	D	0.758	deleterious	N	0.46883757	None	None	N
T/Q	0.3836	ambiguous	0.3277	benign	-0.662	Destabilizing	0.947	D	0.763	deleterious	None	None	None	None	N
T/R	0.414	ambiguous	0.379	ambiguous	-0.285	Destabilizing	0.99	D	0.761	deleterious	None	None	None	None	N
T/S	0.1392	likely_benign	0.1116	benign	-0.627	Destabilizing	0.008	N	0.307	neutral	N	0.448216214	None	None	N
T/V	0.2113	likely_benign	0.1848	benign	-0.392	Destabilizing	0.887	D	0.586	neutral	None	None	None	None	N
T/W	0.8317	likely_pathogenic	0.7662	pathogenic	-0.904	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
T/Y	0.5769	likely_pathogenic	0.4835	ambiguous	-0.67	Destabilizing	0.998	D	0.779	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.