TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3825	11698;11699;11700	chr2:178741760;178741759;178741758	chr2:179606487;179606486;179606485
N2AB	3508	10747;10748;10749	chr2:178741760;178741759;178741758	chr2:179606487;179606486;179606485
N2A	None	None	chr2:None	chr2:None
N2B	3462	10609;10610;10611	chr2:178741760;178741759;178741758	chr2:179606487;179606486;179606485
Novex-1	3587	10984;10985;10986	chr2:178741760;178741759;178741758	chr2:179606487;179606486;179606485
Novex-2	3654	11185;11186;11187	chr2:178741760;178741759;178741758	chr2:179606487;179606486;179606485
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-27
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.6245
• 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/D	None	None	0.081	N	0.347	0.018	None	gnomAD-4.0.0	1.36857E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.31884E-05	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	0.1737	likely_benign	0.1552	benign	-0.69	Destabilizing	0.042	N	0.383	neutral	N	0.499216629	None	None	I
E/C	0.9072	likely_pathogenic	0.887	pathogenic	-0.313	Destabilizing	0.958	D	0.397	neutral	None	None	None	None	I
E/D	0.2712	likely_benign	0.2187	benign	-0.613	Destabilizing	0.081	N	0.347	neutral	N	0.508159963	None	None	I
E/F	0.8807	likely_pathogenic	0.8441	pathogenic	-0.044	Destabilizing	0.667	D	0.401	neutral	None	None	None	None	I
E/G	0.1848	likely_benign	0.1595	benign	-1.009	Destabilizing	0.081	N	0.461	neutral	N	0.486564184	None	None	I
E/H	0.6413	likely_pathogenic	0.5796	pathogenic	-0.018	Destabilizing	0.001	N	0.18	neutral	None	None	None	None	I
E/I	0.5816	likely_pathogenic	0.5128	ambiguous	0.163	Stabilizing	0.667	D	0.448	neutral	None	None	None	None	I
E/K	0.1362	likely_benign	0.1117	benign	0.044	Stabilizing	None	N	0.151	neutral	N	0.415064886	None	None	I
E/L	0.5818	likely_pathogenic	0.5191	ambiguous	0.163	Stabilizing	0.22	N	0.483	neutral	None	None	None	None	I
E/M	0.5626	ambiguous	0.5123	ambiguous	0.354	Stabilizing	0.667	D	0.396	neutral	None	None	None	None	I
E/N	0.3778	ambiguous	0.3074	benign	-0.598	Destabilizing	0.22	N	0.331	neutral	None	None	None	None	I
E/P	0.5379	ambiguous	0.4703	ambiguous	-0.1	Destabilizing	0.364	N	0.473	neutral	None	None	None	None	I
E/Q	0.1767	likely_benign	0.159	benign	-0.476	Destabilizing	None	N	0.12	neutral	N	0.474333883	None	None	I
E/R	0.2715	likely_benign	0.2353	benign	0.351	Stabilizing	0.001	N	0.158	neutral	None	None	None	None	I
E/S	0.3068	likely_benign	0.2506	benign	-0.814	Destabilizing	0.055	N	0.324	neutral	None	None	None	None	I
E/T	0.3248	likely_benign	0.2626	benign	-0.534	Destabilizing	0.22	N	0.445	neutral	None	None	None	None	I
E/V	0.3402	ambiguous	0.3005	benign	-0.1	Destabilizing	0.175	N	0.472	neutral	N	0.506715774	None	None	I
E/W	0.9511	likely_pathogenic	0.9341	pathogenic	0.295	Stabilizing	0.958	D	0.4	neutral	None	None	None	None	I
E/Y	0.7471	likely_pathogenic	0.6942	pathogenic	0.254	Stabilizing	0.331	N	0.478	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.