TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17240	51943;51944;51945	chr2:178609705;178609704;178609703	chr2:179474432;179474431;179474430
N2AB	15599	47020;47021;47022	chr2:178609705;178609704;178609703	chr2:179474432;179474431;179474430
N2A	14672	44239;44240;44241	chr2:178609705;178609704;178609703	chr2:179474432;179474431;179474430
N2B	8175	24748;24749;24750	chr2:178609705;178609704;178609703	chr2:179474432;179474431;179474430
Novex-1	8300	25123;25124;25125	chr2:178609705;178609704;178609703	chr2:179474432;179474431;179474430
Novex-2	8367	25324;25325;25326	chr2:178609705;178609704;178609703	chr2:179474432;179474431;179474430
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-13
• Domain position: 94
• Structural Position: 127
• Q(SASA): 0.209
• Predicted PPI site: N

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
T/I	rs1295961462	0.356	None	N	0.346	0.096	0.204665344411	gnomAD-2.1.1	4.14E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.48E-05	None	0	0	0
T/I	rs1295961462	0.356	None	N	0.346	0.096	0.204665344411	gnomAD-4.0.0	4.14133E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	5.92403E-05	1.67235E-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
T/A	0.079	likely_benign	0.0743	benign	-0.808	Destabilizing	None	N	0.132	neutral	N	0.485155662	None	None	N
T/C	0.2419	likely_benign	0.2378	benign	-0.53	Destabilizing	0.204	N	0.484	neutral	None	None	None	None	N
T/D	0.7566	likely_pathogenic	0.718	pathogenic	-0.601	Destabilizing	0.068	N	0.543	neutral	None	None	None	None	N
T/E	0.4548	ambiguous	0.4305	ambiguous	-0.476	Destabilizing	0.068	N	0.509	neutral	None	None	None	None	N
T/F	0.2367	likely_benign	0.2109	benign	-0.578	Destabilizing	0.035	N	0.598	neutral	None	None	None	None	N
T/G	0.34	likely_benign	0.3022	benign	-1.176	Destabilizing	0.015	N	0.508	neutral	None	None	None	None	N
T/H	0.3164	likely_benign	0.2919	benign	-1.317	Destabilizing	0.747	D	0.553	neutral	None	None	None	None	N
T/I	0.0932	likely_benign	0.0943	benign	0.122	Stabilizing	None	N	0.346	neutral	N	0.42547264	None	None	N
T/K	0.2682	likely_benign	0.2642	benign	-0.642	Destabilizing	0.068	N	0.504	neutral	None	None	None	None	N
T/L	0.0892	likely_benign	0.0883	benign	0.122	Stabilizing	0.003	N	0.381	neutral	None	None	None	None	N
T/M	0.0811	likely_benign	0.0851	benign	0.098	Stabilizing	0.112	N	0.505	neutral	None	None	None	None	N
T/N	0.28	likely_benign	0.256	benign	-0.995	Destabilizing	0.144	N	0.499	neutral	N	0.485849095	None	None	N
T/P	0.719	likely_pathogenic	0.6514	pathogenic	-0.154	Destabilizing	0.144	N	0.549	neutral	N	0.486022454	None	None	N
T/Q	0.2339	likely_benign	0.2343	benign	-0.857	Destabilizing	0.439	N	0.549	neutral	None	None	None	None	N
T/R	0.2253	likely_benign	0.2153	benign	-0.684	Destabilizing	0.204	N	0.547	neutral	None	None	None	None	N
T/S	0.1611	likely_benign	0.1458	benign	-1.248	Destabilizing	0.006	N	0.348	neutral	N	0.485155662	None	None	N
T/V	0.0711	likely_benign	0.0744	benign	-0.154	Destabilizing	None	N	0.133	neutral	None	None	None	None	N
T/W	0.6045	likely_pathogenic	0.5726	pathogenic	-0.692	Destabilizing	0.747	D	0.617	neutral	None	None	None	None	N
T/Y	0.2957	likely_benign	0.2688	benign	-0.362	Destabilizing	0.204	N	0.597	neutral	None	None	None	None	N

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.