TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21908	65947;65948;65949	chr2:178583081;178583080;178583079	chr2:179447808;179447807;179447806
N2AB	20267	61024;61025;61026	chr2:178583081;178583080;178583079	chr2:179447808;179447807;179447806
N2A	19340	58243;58244;58245	chr2:178583081;178583080;178583079	chr2:179447808;179447807;179447806
N2B	12843	38752;38753;38754	chr2:178583081;178583080;178583079	chr2:179447808;179447807;179447806
Novex-1	12968	39127;39128;39129	chr2:178583081;178583080;178583079	chr2:179447808;179447807;179447806
Novex-2	13035	39328;39329;39330	chr2:178583081;178583080;178583079	chr2:179447808;179447807;179447806
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-125
• Domain position: 43
• Structural Position: 109
• Q(SASA): 0.6525
• 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
E/G	None	None	0.505	N	0.403	0.244	0.335164054921	gnomAD-4.0.0	1.59688E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43744E-05	0
E/K	rs2154178693	None	0.013	N	0.265	0.198	0.250039746154	gnomAD-4.0.0	4.79077E-06	None	None	None	None	N	None	0	0	None	0	8.39772E-05	None	0	0	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
E/A	0.1238	likely_benign	0.1311	benign	-0.013	Destabilizing	0.505	D	0.401	neutral	N	0.463731879	None	None	N
E/C	0.8379	likely_pathogenic	0.8416	pathogenic	-0.391	Destabilizing	0.991	D	0.604	neutral	None	None	None	None	N
E/D	0.1086	likely_benign	0.1015	benign	-0.571	Destabilizing	0.003	N	0.233	neutral	N	0.44402861	None	None	N
E/F	0.7887	likely_pathogenic	0.789	pathogenic	-0.142	Destabilizing	0.967	D	0.523	neutral	None	None	None	None	N
E/G	0.1694	likely_benign	0.169	benign	-0.08	Destabilizing	0.505	D	0.403	neutral	N	0.450781224	None	None	N
E/H	0.451	ambiguous	0.4398	ambiguous	0.539	Stabilizing	0.906	D	0.39	neutral	None	None	None	None	N
E/I	0.3867	ambiguous	0.3891	ambiguous	0.102	Stabilizing	0.906	D	0.537	neutral	None	None	None	None	N
E/K	0.1341	likely_benign	0.1393	benign	0.194	Stabilizing	0.013	N	0.265	neutral	N	0.438777506	None	None	N
E/L	0.4355	ambiguous	0.4341	ambiguous	0.102	Stabilizing	0.826	D	0.485	neutral	None	None	None	None	N
E/M	0.5	ambiguous	0.4997	ambiguous	-0.169	Destabilizing	0.973	D	0.496	neutral	None	None	None	None	N
E/N	0.229	likely_benign	0.2291	benign	0.024	Stabilizing	0.404	N	0.377	neutral	None	None	None	None	N
E/P	0.2874	likely_benign	0.2988	benign	0.079	Stabilizing	0.906	D	0.411	neutral	None	None	None	None	N
E/Q	0.1543	likely_benign	0.1512	benign	0.005	Stabilizing	0.031	N	0.279	neutral	N	0.485531303	None	None	N
E/R	0.2578	likely_benign	0.2628	benign	0.413	Stabilizing	0.404	N	0.377	neutral	None	None	None	None	N
E/S	0.1752	likely_benign	0.1787	benign	-0.104	Destabilizing	0.404	N	0.372	neutral	None	None	None	None	N
E/T	0.2033	likely_benign	0.2096	benign	-0.038	Destabilizing	0.826	D	0.385	neutral	None	None	None	None	N
E/V	0.2243	likely_benign	0.2262	benign	0.079	Stabilizing	0.782	D	0.436	neutral	N	0.503463703	None	None	N
E/W	0.9072	likely_pathogenic	0.9036	pathogenic	-0.143	Destabilizing	0.991	D	0.621	neutral	None	None	None	None	N
E/Y	0.6469	likely_pathogenic	0.6472	pathogenic	0.057	Stabilizing	0.967	D	0.478	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.