TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28811	86656;86657;86658	chr2:178559701;178559700;178559699	chr2:179424428;179424427;179424426
N2AB	27170	81733;81734;81735	chr2:178559701;178559700;178559699	chr2:179424428;179424427;179424426
N2A	26243	78952;78953;78954	chr2:178559701;178559700;178559699	chr2:179424428;179424427;179424426
N2B	19746	59461;59462;59463	chr2:178559701;178559700;178559699	chr2:179424428;179424427;179424426
Novex-1	19871	59836;59837;59838	chr2:178559701;178559700;178559699	chr2:179424428;179424427;179424426
Novex-2	19938	60037;60038;60039	chr2:178559701;178559700;178559699	chr2:179424428;179424427;179424426
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-144
• Domain position: 57
• Structural Position: 139
• Q(SASA): 0.2608
• 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/S	rs775103234	-1.037	0.775	N	0.291	0.18	0.286081765059	gnomAD-2.1.1	8.24E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.82E-05	0
T/S	rs775103234	-1.037	0.775	N	0.291	0.18	0.286081765059	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
T/S	rs775103234	-1.037	0.775	N	0.291	0.18	0.286081765059	gnomAD-4.0.0	1.60637E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.88344E-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	0.1071	likely_benign	0.1208	benign	-1.222	Destabilizing	0.948	D	0.463	neutral	N	0.497079223	None	None	N
T/C	0.3103	likely_benign	0.3709	ambiguous	-0.648	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
T/D	0.5912	likely_pathogenic	0.684	pathogenic	-0.342	Destabilizing	0.998	D	0.698	prob.neutral	None	None	None	None	N
T/E	0.4226	ambiguous	0.5197	ambiguous	-0.187	Destabilizing	0.998	D	0.695	prob.neutral	None	None	None	None	N
T/F	0.2409	likely_benign	0.3133	benign	-0.996	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
T/G	0.3361	likely_benign	0.3724	ambiguous	-1.597	Destabilizing	0.992	D	0.585	neutral	None	None	None	None	N
T/H	0.2108	likely_benign	0.275	benign	-1.594	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
T/I	0.1685	likely_benign	0.212	benign	-0.253	Destabilizing	0.998	D	0.77	deleterious	N	0.452041245	None	None	N
T/K	0.2286	likely_benign	0.3091	benign	-0.155	Destabilizing	0.998	D	0.699	prob.neutral	None	None	None	None	N
T/L	0.1271	likely_benign	0.1592	benign	-0.253	Destabilizing	0.996	D	0.58	neutral	None	None	None	None	N
T/M	0.0919	likely_benign	0.0991	benign	-0.232	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
T/N	0.1715	likely_benign	0.2093	benign	-0.541	Destabilizing	0.997	D	0.627	neutral	N	0.491345231	None	None	N
T/P	0.7707	likely_pathogenic	0.8023	pathogenic	-0.546	Destabilizing	0.998	D	0.77	deleterious	D	0.539257585	None	None	N
T/Q	0.209	likely_benign	0.2527	benign	-0.451	Destabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
T/R	0.1677	likely_benign	0.2338	benign	-0.294	Destabilizing	0.999	D	0.774	deleterious	None	None	None	None	N
T/S	0.123	likely_benign	0.1332	benign	-0.975	Destabilizing	0.775	D	0.291	neutral	N	0.49242643	None	None	N
T/V	0.1379	likely_benign	0.1615	benign	-0.546	Destabilizing	0.996	D	0.503	neutral	None	None	None	None	N
T/W	0.5306	ambiguous	0.6274	pathogenic	-0.934	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
T/Y	0.2506	likely_benign	0.3273	benign	-0.62	Destabilizing	1.0	D	0.804	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.