TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24759	74500;74501;74502	chr2:178571857;178571856;178571855	chr2:179436584;179436583;179436582
N2AB	23118	69577;69578;69579	chr2:178571857;178571856;178571855	chr2:179436584;179436583;179436582
N2A	22191	66796;66797;66798	chr2:178571857;178571856;178571855	chr2:179436584;179436583;179436582
N2B	15694	47305;47306;47307	chr2:178571857;178571856;178571855	chr2:179436584;179436583;179436582
Novex-1	15819	47680;47681;47682	chr2:178571857;178571856;178571855	chr2:179436584;179436583;179436582
Novex-2	15886	47881;47882;47883	chr2:178571857;178571856;178571855	chr2:179436584;179436583;179436582
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-133
• Domain position: 44
• Structural Position: 73
• Q(SASA): 0.2916
• 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	rs1421105301	0.051	0.994	N	0.689	0.45	0.412980791724	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
T/I	rs1421105301	0.051	0.994	N	0.689	0.45	0.412980791724	gnomAD-4.0.0	1.59175E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85932E-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	0.689	likely_pathogenic	0.6693	pathogenic	-0.476	Destabilizing	0.825	D	0.441	neutral	N	0.457969839	None	None	N
T/C	0.9571	likely_pathogenic	0.9528	pathogenic	-0.257	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
T/D	0.7696	likely_pathogenic	0.7939	pathogenic	-0.035	Destabilizing	0.991	D	0.669	neutral	None	None	None	None	N
T/E	0.9197	likely_pathogenic	0.9133	pathogenic	-0.107	Destabilizing	0.991	D	0.661	neutral	None	None	None	None	N
T/F	0.947	likely_pathogenic	0.9416	pathogenic	-0.868	Destabilizing	0.995	D	0.751	deleterious	None	None	None	None	N
T/G	0.6934	likely_pathogenic	0.7008	pathogenic	-0.632	Destabilizing	0.938	D	0.586	neutral	None	None	None	None	N
T/H	0.8495	likely_pathogenic	0.8471	pathogenic	-0.977	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
T/I	0.9476	likely_pathogenic	0.9378	pathogenic	-0.178	Destabilizing	0.994	D	0.689	prob.neutral	N	0.468707488	None	None	N
T/K	0.8723	likely_pathogenic	0.8645	pathogenic	-0.56	Destabilizing	0.988	D	0.67	neutral	N	0.45071491	None	None	N
T/L	0.7129	likely_pathogenic	0.682	pathogenic	-0.178	Destabilizing	0.968	D	0.571	neutral	None	None	None	None	N
T/M	0.5019	ambiguous	0.4624	ambiguous	0.104	Stabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
T/N	0.4313	ambiguous	0.4435	ambiguous	-0.291	Destabilizing	0.991	D	0.658	neutral	None	None	None	None	N
T/P	0.8591	likely_pathogenic	0.8608	pathogenic	-0.248	Destabilizing	0.994	D	0.681	prob.neutral	N	0.454615704	None	None	N
T/Q	0.8657	likely_pathogenic	0.8546	pathogenic	-0.548	Destabilizing	0.991	D	0.689	prob.neutral	None	None	None	None	N
T/R	0.8728	likely_pathogenic	0.8617	pathogenic	-0.261	Destabilizing	0.988	D	0.676	prob.neutral	N	0.457324729	None	None	N
T/S	0.378	ambiguous	0.3912	ambiguous	-0.501	Destabilizing	0.234	N	0.301	neutral	N	0.437502496	None	None	N
T/V	0.877	likely_pathogenic	0.8591	pathogenic	-0.248	Destabilizing	0.968	D	0.521	neutral	None	None	None	None	N
T/W	0.9828	likely_pathogenic	0.9817	pathogenic	-0.847	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
T/Y	0.9261	likely_pathogenic	0.921	pathogenic	-0.597	Destabilizing	0.998	D	0.744	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.