TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16287	49084;49085;49086	chr2:178614655;178614654;178614653	chr2:179479382;179479381;179479380
N2AB	14646	44161;44162;44163	chr2:178614655;178614654;178614653	chr2:179479382;179479381;179479380
N2A	13719	41380;41381;41382	chr2:178614655;178614654;178614653	chr2:179479382;179479381;179479380
N2B	7222	21889;21890;21891	chr2:178614655;178614654;178614653	chr2:179479382;179479381;179479380
Novex-1	7347	22264;22265;22266	chr2:178614655;178614654;178614653	chr2:179479382;179479381;179479380
Novex-2	7414	22465;22466;22467	chr2:178614655;178614654;178614653	chr2:179479382;179479381;179479380
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-110
• Domain position: 26
• Structural Position: 43
• Q(SASA): 0.3502
• 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
E/K	None	None	0.581	N	0.556	0.218	0.424194796918	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
E/A	0.1323	likely_benign	0.1363	benign	-0.388	Destabilizing	0.004	N	0.371	neutral	N	0.460702461	None	None	I
E/C	0.8327	likely_pathogenic	0.8299	pathogenic	-0.231	Destabilizing	0.98	D	0.699	prob.neutral	None	None	None	None	I
E/D	0.1514	likely_benign	0.1514	benign	-0.388	Destabilizing	0.581	D	0.477	neutral	N	0.508087025	None	None	I
E/F	0.7187	likely_pathogenic	0.7129	pathogenic	-0.131	Destabilizing	0.929	D	0.709	prob.delet.	None	None	None	None	I
E/G	0.3231	likely_benign	0.3136	benign	-0.609	Destabilizing	0.41	N	0.637	neutral	D	0.604921212	None	None	I
E/H	0.5765	likely_pathogenic	0.5461	ambiguous	0.124	Stabilizing	0.993	D	0.585	neutral	None	None	None	None	I
E/I	0.2582	likely_benign	0.2573	benign	0.167	Stabilizing	0.866	D	0.713	prob.delet.	None	None	None	None	I
E/K	0.2337	likely_benign	0.21	benign	0.147	Stabilizing	0.581	D	0.556	neutral	N	0.484615198	None	None	I
E/L	0.2851	likely_benign	0.2943	benign	0.167	Stabilizing	0.764	D	0.683	prob.neutral	None	None	None	None	I
E/M	0.3729	ambiguous	0.3731	ambiguous	0.148	Stabilizing	0.98	D	0.669	neutral	None	None	None	None	I
E/N	0.3007	likely_benign	0.2998	benign	-0.237	Destabilizing	0.929	D	0.615	neutral	None	None	None	None	I
E/P	0.3942	ambiguous	0.3918	ambiguous	0.002	Stabilizing	0.866	D	0.625	neutral	None	None	None	None	I
E/Q	0.1766	likely_benign	0.1679	benign	-0.169	Destabilizing	0.908	D	0.556	neutral	N	0.506392844	None	None	I
E/R	0.3836	ambiguous	0.3352	benign	0.433	Stabilizing	0.866	D	0.615	neutral	None	None	None	None	I
E/S	0.2236	likely_benign	0.2262	benign	-0.397	Destabilizing	0.48	N	0.549	neutral	None	None	None	None	I
E/T	0.2186	likely_benign	0.2214	benign	-0.215	Destabilizing	0.764	D	0.596	neutral	None	None	None	None	I
E/V	0.1552	likely_benign	0.1573	benign	0.002	Stabilizing	0.709	D	0.637	neutral	N	0.514851936	None	None	I
E/W	0.9266	likely_pathogenic	0.9134	pathogenic	0.043	Stabilizing	0.993	D	0.689	prob.neutral	None	None	None	None	I
E/Y	0.623	likely_pathogenic	0.6001	pathogenic	0.108	Stabilizing	0.929	D	0.686	prob.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.