TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23330	70213;70214;70215	chr2:178576144;178576143;178576142	chr2:179440871;179440870;179440869
N2AB	21689	65290;65291;65292	chr2:178576144;178576143;178576142	chr2:179440871;179440870;179440869
N2A	20762	62509;62510;62511	chr2:178576144;178576143;178576142	chr2:179440871;179440870;179440869
N2B	14265	43018;43019;43020	chr2:178576144;178576143;178576142	chr2:179440871;179440870;179440869
Novex-1	14390	43393;43394;43395	chr2:178576144;178576143;178576142	chr2:179440871;179440870;179440869
Novex-2	14457	43594;43595;43596	chr2:178576144;178576143;178576142	chr2:179440871;179440870;179440869
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: Fn3-57
• Domain position: 91
• Structural Position: 123
• Q(SASA): 0.0832
• 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/T	rs1211020644	-2.885	0.682	N	0.76	0.254	0.665944241059	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
I/T	rs1211020644	-2.885	0.682	N	0.76	0.254	0.665944241059	gnomAD-4.0.0	1.59211E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4339E-05	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	0.6786	likely_pathogenic	0.7116	pathogenic	-2.13	Highly Destabilizing	0.37	N	0.742	deleterious	None	None	None	None	N
I/C	0.772	likely_pathogenic	0.7749	pathogenic	-1.296	Destabilizing	0.996	D	0.707	prob.delet.	None	None	None	None	N
I/D	0.9393	likely_pathogenic	0.9426	pathogenic	-2.187	Highly Destabilizing	0.984	D	0.83	deleterious	None	None	None	None	N
I/E	0.8803	likely_pathogenic	0.8807	pathogenic	-2.0	Highly Destabilizing	0.953	D	0.804	deleterious	None	None	None	None	N
I/F	0.2873	likely_benign	0.2751	benign	-1.222	Destabilizing	0.883	D	0.748	deleterious	N	0.447955216	None	None	N
I/G	0.9101	likely_pathogenic	0.9122	pathogenic	-2.63	Highly Destabilizing	0.953	D	0.752	deleterious	None	None	None	None	N
I/H	0.8074	likely_pathogenic	0.8001	pathogenic	-1.98	Destabilizing	0.996	D	0.839	deleterious	None	None	None	None	N
I/K	0.7894	likely_pathogenic	0.7886	pathogenic	-1.678	Destabilizing	0.953	D	0.805	deleterious	None	None	None	None	N
I/L	0.1124	likely_benign	0.1116	benign	-0.719	Destabilizing	0.162	N	0.433	neutral	N	0.4208059	None	None	N
I/M	0.1454	likely_benign	0.1463	benign	-0.561	Destabilizing	0.938	D	0.709	prob.delet.	N	0.440413168	None	None	N
I/N	0.6082	likely_pathogenic	0.6117	pathogenic	-1.9	Destabilizing	0.979	D	0.831	deleterious	D	0.522047543	None	None	N
I/P	0.9515	likely_pathogenic	0.9508	pathogenic	-1.167	Destabilizing	0.984	D	0.815	deleterious	None	None	None	None	N
I/Q	0.7892	likely_pathogenic	0.7821	pathogenic	-1.815	Destabilizing	0.984	D	0.832	deleterious	None	None	None	None	N
I/R	0.7518	likely_pathogenic	0.7437	pathogenic	-1.349	Destabilizing	0.953	D	0.83	deleterious	None	None	None	None	N
I/S	0.6292	likely_pathogenic	0.6356	pathogenic	-2.567	Highly Destabilizing	0.883	D	0.761	deleterious	N	0.448357861	None	None	N
I/T	0.4777	ambiguous	0.5079	ambiguous	-2.237	Highly Destabilizing	0.682	D	0.76	deleterious	N	0.405895163	None	None	N
I/V	0.1199	likely_benign	0.1313	benign	-1.167	Destabilizing	0.001	N	0.175	neutral	N	0.426846438	None	None	N
I/W	0.9061	likely_pathogenic	0.9027	pathogenic	-1.564	Destabilizing	0.996	D	0.837	deleterious	None	None	None	None	N
I/Y	0.7252	likely_pathogenic	0.7107	pathogenic	-1.242	Destabilizing	0.953	D	0.753	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.