TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28567	85924;85925;85926	chr2:178560433;178560432;178560431	chr2:179425160;179425159;179425158
N2AB	26926	81001;81002;81003	chr2:178560433;178560432;178560431	chr2:179425160;179425159;179425158
N2A	25999	78220;78221;78222	chr2:178560433;178560432;178560431	chr2:179425160;179425159;179425158
N2B	19502	58729;58730;58731	chr2:178560433;178560432;178560431	chr2:179425160;179425159;179425158
Novex-1	19627	59104;59105;59106	chr2:178560433;178560432;178560431	chr2:179425160;179425159;179425158
Novex-2	19694	59305;59306;59307	chr2:178560433;178560432;178560431	chr2:179425160;179425159;179425158
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-96
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.0639
• 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
M/K	None	None	0.684	N	0.785	0.483	0.613916450604	gnomAD-4.0.0	6.84268E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99475E-07	0	0
M/T	None	None	0.684	N	0.746	0.402	0.758402455312	gnomAD-4.0.0	1.36854E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15958E-05	1.65689E-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
M/A	0.7011	likely_pathogenic	0.6694	pathogenic	-1.979	Destabilizing	0.004	N	0.499	neutral	None	None	None	None	N
M/C	0.8519	likely_pathogenic	0.8494	pathogenic	-2.531	Highly Destabilizing	0.953	D	0.796	deleterious	None	None	None	None	N
M/D	0.9974	likely_pathogenic	0.9972	pathogenic	-1.851	Destabilizing	0.953	D	0.807	deleterious	None	None	None	None	N
M/E	0.9734	likely_pathogenic	0.9719	pathogenic	-1.613	Destabilizing	0.742	D	0.778	deleterious	None	None	None	None	N
M/F	0.769	likely_pathogenic	0.7745	pathogenic	-0.696	Destabilizing	0.742	D	0.719	prob.delet.	None	None	None	None	N
M/G	0.9578	likely_pathogenic	0.9551	pathogenic	-2.464	Highly Destabilizing	0.59	D	0.775	deleterious	None	None	None	None	N
M/H	0.9795	likely_pathogenic	0.9808	pathogenic	-2.219	Highly Destabilizing	0.996	D	0.783	deleterious	None	None	None	None	N
M/I	0.5726	likely_pathogenic	0.5381	ambiguous	-0.591	Destabilizing	0.007	N	0.355	neutral	N	0.416708723	None	None	N
M/K	0.9284	likely_pathogenic	0.9288	pathogenic	-1.132	Destabilizing	0.684	D	0.785	deleterious	N	0.504571419	None	None	N
M/L	0.3506	ambiguous	0.3509	ambiguous	-0.591	Destabilizing	0.078	N	0.452	neutral	N	0.452477522	None	None	N
M/N	0.971	likely_pathogenic	0.9695	pathogenic	-1.566	Destabilizing	0.953	D	0.812	deleterious	None	None	None	None	N
M/P	0.9978	likely_pathogenic	0.9973	pathogenic	-1.035	Destabilizing	0.953	D	0.807	deleterious	None	None	None	None	N
M/Q	0.8316	likely_pathogenic	0.8387	pathogenic	-1.226	Destabilizing	0.953	D	0.721	prob.delet.	None	None	None	None	N
M/R	0.9359	likely_pathogenic	0.932	pathogenic	-1.379	Destabilizing	0.939	D	0.833	deleterious	N	0.49305053	None	None	N
M/S	0.8697	likely_pathogenic	0.851	pathogenic	-2.142	Highly Destabilizing	0.59	D	0.733	prob.delet.	None	None	None	None	N
M/T	0.8032	likely_pathogenic	0.7707	pathogenic	-1.761	Destabilizing	0.684	D	0.746	deleterious	N	0.492543551	None	None	N
M/V	0.136	likely_benign	0.1339	benign	-1.035	Destabilizing	0.164	N	0.44	neutral	N	0.376072822	None	None	N
M/W	0.9897	likely_pathogenic	0.9888	pathogenic	-1.009	Destabilizing	0.996	D	0.765	deleterious	None	None	None	None	N
M/Y	0.9766	likely_pathogenic	0.9768	pathogenic	-0.926	Destabilizing	0.984	D	0.827	deleterious	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.