TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5256	15991;15992;15993	chr2:178733623;178733622;178733621	chr2:179598350;179598349;179598348
N2AB	4939	15040;15041;15042	chr2:178733623;178733622;178733621	chr2:179598350;179598349;179598348
N2A	4012	12259;12260;12261	chr2:178733623;178733622;178733621	chr2:179598350;179598349;179598348
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-35
• Domain position: 89
• Structural Position: 175
• Q(SASA): 0.3234
• 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/T	rs773177460	-0.672	None	N	0.111	0.109	0.374970422459	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	4.67E-05	0	0
I/T	rs773177460	-0.672	None	N	0.111	0.109	0.374970422459	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	9.41E-05	0	0	0	0
I/T	rs773177460	-0.672	None	N	0.111	0.109	0.374970422459	gnomAD-4.0.0	2.48319E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.56348E-05	0	1.69832E-06	0	1.60514E-05

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	0.0973	likely_benign	0.1155	benign	-1.257	Destabilizing	None	N	0.112	neutral	None	None	None	None	I
I/C	0.4227	ambiguous	0.4731	ambiguous	-0.842	Destabilizing	0.54	D	0.358	neutral	None	None	None	None	I
I/D	0.31	likely_benign	0.3773	ambiguous	-0.627	Destabilizing	0.142	N	0.455	neutral	None	None	None	None	I
I/E	0.2358	likely_benign	0.273	benign	-0.65	Destabilizing	0.064	N	0.402	neutral	None	None	None	None	I
I/F	0.0902	likely_benign	0.1005	benign	-0.828	Destabilizing	None	N	0.107	neutral	None	None	None	None	I
I/G	0.2965	likely_benign	0.3562	ambiguous	-1.541	Destabilizing	0.033	N	0.384	neutral	None	None	None	None	I
I/H	0.1757	likely_benign	0.1952	benign	-0.703	Destabilizing	0.781	D	0.433	neutral	None	None	None	None	I
I/K	0.1277	likely_benign	0.1417	benign	-0.884	Destabilizing	0.049	N	0.394	neutral	N	0.489306263	None	None	I
I/L	0.0747	likely_benign	0.0808	benign	-0.576	Destabilizing	0.002	N	0.169	neutral	N	0.492490801	None	None	I
I/M	0.0699	likely_benign	0.0745	benign	-0.531	Destabilizing	0.005	N	0.169	neutral	N	0.512590657	None	None	I
I/N	0.1085	likely_benign	0.1211	benign	-0.684	Destabilizing	0.142	N	0.451	neutral	None	None	None	None	I
I/P	0.6227	likely_pathogenic	0.7522	pathogenic	-0.77	Destabilizing	0.251	N	0.492	neutral	None	None	None	None	I
I/Q	0.1513	likely_benign	0.1711	benign	-0.865	Destabilizing	0.251	N	0.509	neutral	None	None	None	None	I
I/R	0.0896	likely_benign	0.0996	benign	-0.291	Destabilizing	0.111	N	0.491	neutral	N	0.487512472	None	None	I
I/S	0.0991	likely_benign	0.1125	benign	-1.259	Destabilizing	0.003	N	0.151	neutral	None	None	None	None	I
I/T	0.0623	likely_benign	0.0671	benign	-1.166	Destabilizing	None	N	0.111	neutral	N	0.399463836	None	None	I
I/V	0.0648	likely_benign	0.0731	benign	-0.77	Destabilizing	0.005	N	0.182	neutral	N	0.484289497	None	None	I
I/W	0.4298	ambiguous	0.472	ambiguous	-0.867	Destabilizing	0.931	D	0.425	neutral	None	None	None	None	I
I/Y	0.2616	likely_benign	0.2827	benign	-0.652	Destabilizing	0.076	N	0.383	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.