TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34962	105109;105110;105111	chr2:178531731;178531730;178531729	chr2:179396458;179396457;179396456
N2AB	33321	100186;100187;100188	chr2:178531731;178531730;178531729	chr2:179396458;179396457;179396456
N2A	32394	97405;97406;97407	chr2:178531731;178531730;178531729	chr2:179396458;179396457;179396456
N2B	25897	77914;77915;77916	chr2:178531731;178531730;178531729	chr2:179396458;179396457;179396456
Novex-1	26022	78289;78290;78291	chr2:178531731;178531730;178531729	chr2:179396458;179396457;179396456
Novex-2	26089	78490;78491;78492	chr2:178531731;178531730;178531729	chr2:179396458;179396457;179396456
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-163
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.429
• Predicted PPI site: I

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/N	rs746239963	-1.103	0.988	N	0.589	0.439	0.778651688032	gnomAD-2.1.1	4.01E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.86E-06	0
I/N	rs746239963	-1.103	0.988	N	0.589	0.439	0.778651688032	gnomAD-4.0.0	2.05242E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.6982E-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	0.8483	likely_pathogenic	0.9417	pathogenic	-2.321	Highly Destabilizing	0.863	D	0.449	neutral	None	None	None	None	I
I/C	0.9437	likely_pathogenic	0.9786	pathogenic	-1.316	Destabilizing	0.999	D	0.543	neutral	None	None	None	None	I
I/D	0.9833	likely_pathogenic	0.9941	pathogenic	-2.258	Highly Destabilizing	0.969	D	0.582	neutral	None	None	None	None	I
I/E	0.9665	likely_pathogenic	0.9879	pathogenic	-2.14	Highly Destabilizing	0.969	D	0.578	neutral	None	None	None	None	I
I/F	0.4495	ambiguous	0.638	pathogenic	-1.403	Destabilizing	0.996	D	0.482	neutral	N	0.427084085	None	None	I
I/G	0.9716	likely_pathogenic	0.9891	pathogenic	-2.763	Highly Destabilizing	0.969	D	0.532	neutral	None	None	None	None	I
I/H	0.884	likely_pathogenic	0.9511	pathogenic	-2.07	Highly Destabilizing	0.999	D	0.612	neutral	None	None	None	None	I
I/K	0.9247	likely_pathogenic	0.9693	pathogenic	-1.712	Destabilizing	0.939	D	0.582	neutral	None	None	None	None	I
I/L	0.2744	likely_benign	0.3988	ambiguous	-1.094	Destabilizing	0.675	D	0.39	neutral	N	0.421176833	None	None	I
I/M	0.3251	likely_benign	0.493	ambiguous	-0.823	Destabilizing	0.996	D	0.497	neutral	N	0.43048975	None	None	I
I/N	0.8264	likely_pathogenic	0.9297	pathogenic	-1.703	Destabilizing	0.988	D	0.589	neutral	N	0.428236092	None	None	I
I/P	0.9817	likely_pathogenic	0.9891	pathogenic	-1.48	Destabilizing	0.997	D	0.593	neutral	None	None	None	None	I
I/Q	0.8889	likely_pathogenic	0.9503	pathogenic	-1.75	Destabilizing	0.997	D	0.603	neutral	None	None	None	None	I
I/R	0.8524	likely_pathogenic	0.9375	pathogenic	-1.197	Destabilizing	0.991	D	0.594	neutral	None	None	None	None	I
I/S	0.753	likely_pathogenic	0.8896	pathogenic	-2.358	Highly Destabilizing	0.852	D	0.483	neutral	N	0.38854434	None	None	I
I/T	0.6308	likely_pathogenic	0.8431	pathogenic	-2.126	Highly Destabilizing	0.021	N	0.329	neutral	N	0.324455576	None	None	I
I/V	0.2081	likely_benign	0.3567	ambiguous	-1.48	Destabilizing	0.675	D	0.388	neutral	N	0.433644698	None	None	I
I/W	0.9616	likely_pathogenic	0.9792	pathogenic	-1.684	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	I
I/Y	0.8509	likely_pathogenic	0.9128	pathogenic	-1.455	Destabilizing	0.997	D	0.552	neutral	None	None	None	None	I

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.