TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20563	61912;61913;61914	chr2:178590038;178590037;178590036	chr2:179454765;179454764;179454763
N2AB	18922	56989;56990;56991	chr2:178590038;178590037;178590036	chr2:179454765;179454764;179454763
N2A	17995	54208;54209;54210	chr2:178590038;178590037;178590036	chr2:179454765;179454764;179454763
N2B	11498	34717;34718;34719	chr2:178590038;178590037;178590036	chr2:179454765;179454764;179454763
Novex-1	11623	35092;35093;35094	chr2:178590038;178590037;178590036	chr2:179454765;179454764;179454763
Novex-2	11690	35293;35294;35295	chr2:178590038;178590037;178590036	chr2:179454765;179454764;179454763
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-121
• Domain position: 85
• Structural Position: 173
• Q(SASA): 0.3793
• 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/M	None	None	0.916	N	0.558	0.201	0.592827455569	gnomAD-4.0.0	6.8451E-07	None	None	None	None	I	None	0	0	None	0	2.52755E-05	None	0	0	0	0	0
I/V	rs1278288633	-0.836	0.002	N	0.128	0.095	0.461058313273	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	5.61E-05	None	0	None	0	0	0
I/V	rs1278288633	-0.836	0.002	N	0.128	0.095	0.461058313273	gnomAD-4.0.0	1.59279E-06	None	None	None	None	I	None	0	0	None	0	2.78195E-05	None	0	0	0	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	0.2897	likely_benign	0.2846	benign	-1.596	Destabilizing	0.25	N	0.461	neutral	None	None	None	None	I
I/C	0.7029	likely_pathogenic	0.7097	pathogenic	-0.994	Destabilizing	0.977	D	0.57	neutral	None	None	None	None	I
I/D	0.7132	likely_pathogenic	0.6664	pathogenic	-0.757	Destabilizing	0.92	D	0.617	neutral	None	None	None	None	I
I/E	0.6018	likely_pathogenic	0.5683	pathogenic	-0.741	Destabilizing	0.92	D	0.62	neutral	None	None	None	None	I
I/F	0.1773	likely_benign	0.1828	benign	-1.065	Destabilizing	0.81	D	0.555	neutral	N	0.463986248	None	None	I
I/G	0.6773	likely_pathogenic	0.6734	pathogenic	-1.931	Destabilizing	0.766	D	0.616	neutral	None	None	None	None	I
I/H	0.4892	ambiguous	0.4751	ambiguous	-1.096	Destabilizing	0.992	D	0.594	neutral	None	None	None	None	I
I/K	0.4311	ambiguous	0.4095	ambiguous	-0.988	Destabilizing	0.85	D	0.626	neutral	None	None	None	None	I
I/L	0.1104	likely_benign	0.1199	benign	-0.749	Destabilizing	0.099	N	0.267	neutral	N	0.441186746	None	None	I
I/M	0.1056	likely_benign	0.1067	benign	-0.609	Destabilizing	0.916	D	0.558	neutral	N	0.479859777	None	None	I
I/N	0.2822	likely_benign	0.2611	benign	-0.824	Destabilizing	0.896	D	0.619	neutral	N	0.409882404	None	None	I
I/P	0.8141	likely_pathogenic	0.8155	pathogenic	-1.0	Destabilizing	0.972	D	0.621	neutral	None	None	None	None	I
I/Q	0.4593	ambiguous	0.4298	ambiguous	-0.973	Destabilizing	0.972	D	0.623	neutral	None	None	None	None	I
I/R	0.3366	likely_benign	0.3323	benign	-0.446	Destabilizing	0.92	D	0.625	neutral	None	None	None	None	I
I/S	0.2823	likely_benign	0.2627	benign	-1.508	Destabilizing	0.379	N	0.586	neutral	N	0.425830505	None	None	I
I/T	0.1534	likely_benign	0.15	benign	-1.371	Destabilizing	0.007	N	0.241	neutral	N	0.385042675	None	None	I
I/V	0.0675	likely_benign	0.0711	benign	-1.0	Destabilizing	0.002	N	0.128	neutral	N	0.455366765	None	None	I
I/W	0.7538	likely_pathogenic	0.7685	pathogenic	-1.121	Destabilizing	0.992	D	0.603	neutral	None	None	None	None	I
I/Y	0.4916	ambiguous	0.4999	ambiguous	-0.89	Destabilizing	0.92	D	0.611	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.