TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25143	75652;75653;75654	chr2:178570705;178570704;178570703	chr2:179435432;179435431;179435430
N2AB	23502	70729;70730;70731	chr2:178570705;178570704;178570703	chr2:179435432;179435431;179435430
N2A	22575	67948;67949;67950	chr2:178570705;178570704;178570703	chr2:179435432;179435431;179435430
N2B	16078	48457;48458;48459	chr2:178570705;178570704;178570703	chr2:179435432;179435431;179435430
Novex-1	16203	48832;48833;48834	chr2:178570705;178570704;178570703	chr2:179435432;179435431;179435430
Novex-2	16270	49033;49034;49035	chr2:178570705;178570704;178570703	chr2:179435432;179435431;179435430
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-134
• Domain position: 33
• Structural Position: 46
• Q(SASA): 0.1906
• 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
I/T	rs988443056	None	None	N	0.385	0.198	0.567207890759	gnomAD-4.0.0	1.59168E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41313E-04	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	0.2532	likely_benign	0.2778	benign	-2.011	Highly Destabilizing	0.007	N	0.555	neutral	None	None	None	None	N
I/C	0.5424	ambiguous	0.5919	pathogenic	-1.237	Destabilizing	0.356	N	0.688	prob.neutral	None	None	None	None	N
I/D	0.8526	likely_pathogenic	0.8822	pathogenic	-1.581	Destabilizing	0.072	N	0.727	prob.delet.	None	None	None	None	N
I/E	0.7687	likely_pathogenic	0.8078	pathogenic	-1.515	Destabilizing	0.072	N	0.713	prob.delet.	None	None	None	None	N
I/F	0.1758	likely_benign	0.1954	benign	-1.302	Destabilizing	0.171	N	0.597	neutral	N	0.514986576	None	None	N
I/G	0.6358	likely_pathogenic	0.6741	pathogenic	-2.419	Highly Destabilizing	0.038	N	0.692	prob.neutral	None	None	None	None	N
I/H	0.6128	likely_pathogenic	0.6765	pathogenic	-1.711	Destabilizing	0.676	D	0.785	deleterious	None	None	None	None	N
I/K	0.5527	ambiguous	0.6291	pathogenic	-1.467	Destabilizing	0.038	N	0.709	prob.delet.	None	None	None	None	N
I/L	0.1051	likely_benign	0.1166	benign	-0.92	Destabilizing	0.005	N	0.388	neutral	N	0.500134324	None	None	N
I/M	0.1087	likely_benign	0.1155	benign	-0.719	Destabilizing	0.005	N	0.436	neutral	N	0.51583595	None	None	N
I/N	0.405	ambiguous	0.4722	ambiguous	-1.33	Destabilizing	0.029	N	0.751	deleterious	D	0.550741013	None	None	N
I/P	0.7014	likely_pathogenic	0.7311	pathogenic	-1.255	Destabilizing	0.356	N	0.756	deleterious	None	None	None	None	N
I/Q	0.5823	likely_pathogenic	0.635	pathogenic	-1.425	Destabilizing	0.214	N	0.758	deleterious	None	None	None	None	N
I/R	0.4516	ambiguous	0.5351	ambiguous	-0.955	Destabilizing	0.214	N	0.756	deleterious	None	None	None	None	N
I/S	0.2851	likely_benign	0.3289	benign	-1.996	Destabilizing	0.001	N	0.511	neutral	N	0.520862379	None	None	N
I/T	0.1855	likely_benign	0.2001	benign	-1.803	Destabilizing	None	N	0.385	neutral	N	0.518140128	None	None	N
I/V	0.0691	likely_benign	0.0684	benign	-1.255	Destabilizing	None	N	0.181	neutral	N	0.434252413	None	None	N
I/W	0.8057	likely_pathogenic	0.8411	pathogenic	-1.462	Destabilizing	0.864	D	0.776	deleterious	None	None	None	None	N
I/Y	0.5156	ambiguous	0.6101	pathogenic	-1.236	Destabilizing	0.356	N	0.672	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.