TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3879	11860;11861;11862	chr2:178741598;178741597;178741596	chr2:179606325;179606324;179606323
N2AB	3562	10909;10910;10911	chr2:178741598;178741597;178741596	chr2:179606325;179606324;179606323
N2A	None	None	chr2:None	chr2:None
N2B	3516	10771;10772;10773	chr2:178741598;178741597;178741596	chr2:179606325;179606324;179606323
Novex-1	3641	11146;11147;11148	chr2:178741598;178741597;178741596	chr2:179606325;179606324;179606323
Novex-2	3708	11347;11348;11349	chr2:178741598;178741597;178741596	chr2:179606325;179606324;179606323
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-27
• Domain position: 60
• Structural Position: 140
• Q(SASA): 0.0332
• 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
I/V	rs765448965	-1.617	0.58	D	0.337	0.446	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
I/V	rs765448965	-1.617	0.58	D	0.337	0.446	None	gnomAD-4.0.0	3.42096E-06	None	None	None	None	N	None	0	0	None	0	2.51991E-05	None	0	0	3.5978E-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
I/A	0.954	likely_pathogenic	0.9358	pathogenic	-2.963	Highly Destabilizing	0.953	D	0.705	prob.neutral	None	None	None	None	N
I/C	0.9516	likely_pathogenic	0.9329	pathogenic	-2.163	Highly Destabilizing	0.999	D	0.78	deleterious	None	None	None	None	N
I/D	0.9954	likely_pathogenic	0.993	pathogenic	-3.504	Highly Destabilizing	0.998	D	0.875	deleterious	None	None	None	None	N
I/E	0.9915	likely_pathogenic	0.9872	pathogenic	-3.211	Highly Destabilizing	0.998	D	0.872	deleterious	None	None	None	None	N
I/F	0.4802	ambiguous	0.4056	ambiguous	-1.765	Destabilizing	0.982	D	0.707	prob.neutral	D	0.605496333	None	None	N
I/G	0.9917	likely_pathogenic	0.9866	pathogenic	-3.569	Highly Destabilizing	0.993	D	0.875	deleterious	None	None	None	None	N
I/H	0.9616	likely_pathogenic	0.9435	pathogenic	-3.057	Highly Destabilizing	0.999	D	0.869	deleterious	None	None	None	None	N
I/K	0.9615	likely_pathogenic	0.9434	pathogenic	-2.425	Highly Destabilizing	0.993	D	0.873	deleterious	None	None	None	None	N
I/L	0.2652	likely_benign	0.2308	benign	-1.161	Destabilizing	0.02	N	0.287	neutral	D	0.546839213	None	None	N
I/M	0.3549	ambiguous	0.3045	benign	-1.142	Destabilizing	0.982	D	0.692	prob.neutral	D	0.705813246	None	None	N
I/N	0.9295	likely_pathogenic	0.9079	pathogenic	-2.996	Highly Destabilizing	0.997	D	0.883	deleterious	D	0.796971146	None	None	N
I/P	0.9935	likely_pathogenic	0.9911	pathogenic	-1.749	Destabilizing	0.998	D	0.88	deleterious	None	None	None	None	N
I/Q	0.9752	likely_pathogenic	0.9639	pathogenic	-2.735	Highly Destabilizing	0.998	D	0.894	deleterious	None	None	None	None	N
I/R	0.9392	likely_pathogenic	0.9125	pathogenic	-2.219	Highly Destabilizing	0.993	D	0.875	deleterious	None	None	None	None	N
I/S	0.9242	likely_pathogenic	0.8979	pathogenic	-3.66	Highly Destabilizing	0.991	D	0.835	deleterious	D	0.796971146	None	None	N
I/T	0.9174	likely_pathogenic	0.894	pathogenic	-3.209	Highly Destabilizing	0.991	D	0.761	deleterious	D	0.74085278	None	None	N
I/V	0.1966	likely_benign	0.1781	benign	-1.749	Destabilizing	0.58	D	0.337	neutral	D	0.547806922	None	None	N
I/W	0.9826	likely_pathogenic	0.9725	pathogenic	-2.206	Highly Destabilizing	0.999	D	0.859	deleterious	None	None	None	None	N
I/Y	0.9049	likely_pathogenic	0.8745	pathogenic	-1.963	Destabilizing	0.993	D	0.78	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.