TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8274	25045;25046;25047	chr2:178718186;178718185;178718184	chr2:179582913;179582912;179582911
N2AB	7957	24094;24095;24096	chr2:178718186;178718185;178718184	chr2:179582913;179582912;179582911
N2A	7030	21313;21314;21315	chr2:178718186;178718185;178718184	chr2:179582913;179582912;179582911
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-68
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.8341
• 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	rs72648981	0.792	0.967	N	0.604	0.248	None	gnomAD-2.1.1	2.30508E-03	None	None	None	None	I	None	4.97471E-04	7.95635E-04	None	1.16822E-03	0	None	0	None	4.02228E-03	3.75627E-03	2.9855E-03
E/K	rs72648981	0.792	0.967	N	0.604	0.248	None	gnomAD-3.1.2	2.32668E-03	None	None	None	None	I	None	6.75774E-04	1.17878E-03	0	5.76701E-04	0	None	3.9548E-03	0	3.82241E-03	0	1.91022E-03
E/K	rs72648981	0.792	0.967	N	0.604	0.248	None	1000 genomes	5.99042E-04	None	None	None	None	I	None	0	0	None	None	0	3E-03	None	None	None	0	None
E/K	rs72648981	0.792	0.967	N	0.604	0.248	None	gnomAD-4.0.0	2.97975E-03	None	None	None	None	I	None	5.33988E-04	8.52016E-04	None	8.12623E-04	0	None	3.21302E-03	0	3.69014E-03	0	2.16485E-03

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	0.1947	likely_benign	0.2035	benign	-0.443	Destabilizing	0.97	D	0.611	neutral	N	0.477302262	None	None	I
E/C	0.9027	likely_pathogenic	0.9188	pathogenic	-0.203	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
E/D	0.1988	likely_benign	0.214	benign	-0.466	Destabilizing	0.805	D	0.556	neutral	N	0.438842661	None	None	I
E/F	0.7967	likely_pathogenic	0.8256	pathogenic	-0.18	Destabilizing	0.998	D	0.667	neutral	None	None	None	None	I
E/G	0.2843	likely_benign	0.3374	benign	-0.665	Destabilizing	0.995	D	0.537	neutral	N	0.51586065	None	None	I
E/H	0.5054	ambiguous	0.5337	ambiguous	0.087	Stabilizing	0.999	D	0.553	neutral	None	None	None	None	I
E/I	0.4359	ambiguous	0.4391	ambiguous	0.12	Stabilizing	0.949	D	0.561	neutral	None	None	None	None	I
E/K	0.1874	likely_benign	0.2075	benign	0.211	Stabilizing	0.967	D	0.604	neutral	N	0.447152713	None	None	I
E/L	0.4773	ambiguous	0.4881	ambiguous	0.12	Stabilizing	0.949	D	0.584	neutral	None	None	None	None	I
E/M	0.5329	ambiguous	0.5406	ambiguous	0.148	Stabilizing	0.994	D	0.637	neutral	None	None	None	None	I
E/N	0.355	ambiguous	0.3607	ambiguous	-0.22	Destabilizing	0.992	D	0.567	neutral	None	None	None	None	I
E/P	0.6985	likely_pathogenic	0.7022	pathogenic	-0.047	Destabilizing	0.992	D	0.585	neutral	None	None	None	None	I
E/Q	0.1682	likely_benign	0.1684	benign	-0.171	Destabilizing	0.793	D	0.24	neutral	N	0.43257005	None	None	I
E/R	0.3226	likely_benign	0.3588	ambiguous	0.503	Stabilizing	0.996	D	0.561	neutral	None	None	None	None	I
E/S	0.2449	likely_benign	0.2464	benign	-0.376	Destabilizing	0.977	D	0.555	neutral	None	None	None	None	I
E/T	0.2348	likely_benign	0.2314	benign	-0.192	Destabilizing	0.983	D	0.569	neutral	None	None	None	None	I
E/V	0.232	likely_benign	0.2342	benign	-0.047	Destabilizing	0.209	N	0.315	neutral	N	0.450499663	None	None	I
E/W	0.9178	likely_pathogenic	0.9375	pathogenic	0.017	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
E/Y	0.7068	likely_pathogenic	0.7466	pathogenic	0.073	Stabilizing	1.0	D	0.643	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.