TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16237	48934;48935;48936	chr2:178614898;178614897;178614896	chr2:179479625;179479624;179479623
N2AB	14596	44011;44012;44013	chr2:178614898;178614897;178614896	chr2:179479625;179479624;179479623
N2A	13669	41230;41231;41232	chr2:178614898;178614897;178614896	chr2:179479625;179479624;179479623
N2B	7172	21739;21740;21741	chr2:178614898;178614897;178614896	chr2:179479625;179479624;179479623
Novex-1	7297	22114;22115;22116	chr2:178614898;178614897;178614896	chr2:179479625;179479624;179479623
Novex-2	7364	22315;22316;22317	chr2:178614898;178614897;178614896	chr2:179479625;179479624;179479623
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-5
• Domain position: 83
• Structural Position: 117
• Q(SASA): 0.2909
• 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
A/S	None	None	0.505	N	0.669	0.099	0.215109475489	gnomAD-4.0.0	1.67126E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.99846E-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
A/C	0.4552	ambiguous	0.4238	ambiguous	-0.999	Destabilizing	0.991	D	0.708	prob.delet.	None	None	None	None	N
A/D	0.4871	ambiguous	0.469	ambiguous	-1.286	Destabilizing	0.782	D	0.812	deleterious	N	0.471125113	None	None	N
A/E	0.3162	likely_benign	0.3006	benign	-1.372	Destabilizing	0.826	D	0.705	prob.neutral	None	None	None	None	N
A/F	0.3015	likely_benign	0.2987	benign	-1.251	Destabilizing	0.826	D	0.81	deleterious	None	None	None	None	N
A/G	0.1973	likely_benign	0.184	benign	-1.196	Destabilizing	0.505	D	0.647	neutral	N	0.490165466	None	None	N
A/H	0.5163	ambiguous	0.5114	ambiguous	-1.203	Destabilizing	0.991	D	0.807	deleterious	None	None	None	None	N
A/I	0.1869	likely_benign	0.1961	benign	-0.665	Destabilizing	0.404	N	0.671	neutral	None	None	None	None	N
A/K	0.5958	likely_pathogenic	0.5614	ambiguous	-1.277	Destabilizing	0.826	D	0.706	prob.neutral	None	None	None	None	N
A/L	0.1558	likely_benign	0.1582	benign	-0.665	Destabilizing	0.004	N	0.403	neutral	None	None	None	None	N
A/M	0.2157	likely_benign	0.2275	benign	-0.476	Destabilizing	0.826	D	0.751	deleterious	None	None	None	None	N
A/N	0.299	likely_benign	0.3253	benign	-0.94	Destabilizing	0.906	D	0.812	deleterious	None	None	None	None	N
A/P	0.0952	likely_benign	0.0921	benign	-0.741	Destabilizing	0.007	N	0.381	neutral	N	0.453364097	None	None	N
A/Q	0.3386	likely_benign	0.3356	benign	-1.212	Destabilizing	0.906	D	0.747	deleterious	None	None	None	None	N
A/R	0.565	likely_pathogenic	0.5156	ambiguous	-0.767	Destabilizing	0.906	D	0.745	deleterious	None	None	None	None	N
A/S	0.1073	likely_benign	0.1111	benign	-1.245	Destabilizing	0.505	D	0.669	neutral	N	0.470935537	None	None	N
A/T	0.1139	likely_benign	0.1197	benign	-1.251	Destabilizing	0.505	D	0.664	neutral	N	0.46196181	None	None	N
A/V	0.1145	likely_benign	0.1215	benign	-0.741	Destabilizing	0.003	N	0.347	neutral	N	0.418968234	None	None	N
A/W	0.753	likely_pathogenic	0.7188	pathogenic	-1.456	Destabilizing	0.991	D	0.795	deleterious	None	None	None	None	N
A/Y	0.4666	ambiguous	0.4512	ambiguous	-1.126	Destabilizing	0.967	D	0.812	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.