TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19398	58417;58418;58419	chr2:178594201;178594200;178594199	chr2:179458928;179458927;179458926
N2AB	17757	53494;53495;53496	chr2:178594201;178594200;178594199	chr2:179458928;179458927;179458926
N2A	16830	50713;50714;50715	chr2:178594201;178594200;178594199	chr2:179458928;179458927;179458926
N2B	10333	31222;31223;31224	chr2:178594201;178594200;178594199	chr2:179458928;179458927;179458926
Novex-1	10458	31597;31598;31599	chr2:178594201;178594200;178594199	chr2:179458928;179458927;179458926
Novex-2	10525	31798;31799;31800	chr2:178594201;178594200;178594199	chr2:179458928;179458927;179458926
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-118
• Domain position: 8
• Structural Position: 16
• Q(SASA): 0.2135
• 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/V	rs375724247	None	None	N	0.155	0.079	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/V	rs375724247	None	None	N	0.155	0.079	None	gnomAD-4.0.0	3.04509E-06	None	None	None	None	I	None	3.49467E-05	0	None	0	0	None	0	0	1.20497E-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	0.4335	ambiguous	0.3938	ambiguous	-2.377	Highly Destabilizing	0.007	N	0.271	neutral	None	None	None	None	I
I/C	0.6454	likely_pathogenic	0.6175	pathogenic	-1.646	Destabilizing	0.356	N	0.446	neutral	None	None	None	None	I
I/D	0.9554	likely_pathogenic	0.9463	pathogenic	-2.213	Highly Destabilizing	0.356	N	0.56	neutral	None	None	None	None	I
I/E	0.8932	likely_pathogenic	0.8767	pathogenic	-2.04	Highly Destabilizing	0.136	N	0.537	neutral	None	None	None	None	I
I/F	0.3611	ambiguous	0.3381	benign	-1.407	Destabilizing	0.055	N	0.453	neutral	D	0.527096364	None	None	I
I/G	0.7957	likely_pathogenic	0.7652	pathogenic	-2.883	Highly Destabilizing	0.136	N	0.502	neutral	None	None	None	None	I
I/H	0.8717	likely_pathogenic	0.8439	pathogenic	-2.187	Highly Destabilizing	0.864	D	0.505	neutral	None	None	None	None	I
I/K	0.7979	likely_pathogenic	0.7512	pathogenic	-1.791	Destabilizing	0.136	N	0.547	neutral	None	None	None	None	I
I/L	0.1489	likely_benign	0.1438	benign	-0.948	Destabilizing	0.002	N	0.174	neutral	N	0.478224982	None	None	I
I/M	0.1653	likely_benign	0.1582	benign	-0.857	Destabilizing	0.171	N	0.452	neutral	D	0.534907771	None	None	I
I/N	0.6996	likely_pathogenic	0.6639	pathogenic	-1.944	Destabilizing	0.56	D	0.541	neutral	N	0.502270236	None	None	I
I/P	0.9547	likely_pathogenic	0.9405	pathogenic	-1.4	Destabilizing	0.628	D	0.563	neutral	None	None	None	None	I
I/Q	0.7955	likely_pathogenic	0.7612	pathogenic	-1.892	Destabilizing	0.628	D	0.519	neutral	None	None	None	None	I
I/R	0.7252	likely_pathogenic	0.6563	pathogenic	-1.398	Destabilizing	0.356	N	0.532	neutral	None	None	None	None	I
I/S	0.5673	likely_pathogenic	0.5155	ambiguous	-2.693	Highly Destabilizing	0.055	N	0.449	neutral	D	0.534907771	None	None	I
I/T	0.3898	ambiguous	0.3516	ambiguous	-2.379	Highly Destabilizing	0.012	N	0.378	neutral	D	0.526402931	None	None	I
I/V	0.0564	likely_benign	0.0573	benign	-1.4	Destabilizing	None	N	0.155	neutral	N	0.373726816	None	None	I
I/W	0.9506	likely_pathogenic	0.9378	pathogenic	-1.695	Destabilizing	0.864	D	0.517	neutral	None	None	None	None	I
I/Y	0.8101	likely_pathogenic	0.7923	pathogenic	-1.425	Destabilizing	0.356	N	0.487	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.