TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15523	46792;46793;46794	chr2:178619750;178619749;178619748	chr2:179484477;179484476;179484475
N2AB	13882	41869;41870;41871	chr2:178619750;178619749;178619748	chr2:179484477;179484476;179484475
N2A	12955	39088;39089;39090	chr2:178619750;178619749;178619748	chr2:179484477;179484476;179484475
N2B	6458	19597;19598;19599	chr2:178619750;178619749;178619748	chr2:179484477;179484476;179484475
Novex-1	6583	19972;19973;19974	chr2:178619750;178619749;178619748	chr2:179484477;179484476;179484475
Novex-2	6650	20173;20174;20175	chr2:178619750;178619749;178619748	chr2:179484477;179484476;179484475
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-107
• Domain position: 44
• Structural Position: 111
• Q(SASA): 1.1049
• 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
D/E	rs1553713980	None	1.0	N	0.418	0.267	0.355034743287	gnomAD-4.0.0	1.4345E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	2.17812E-03	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
D/A	0.4314	ambiguous	0.446	ambiguous	0.073	Stabilizing	1.0	D	0.607	neutral	D	0.588732174	None	None	N
D/C	0.8886	likely_pathogenic	0.9048	pathogenic	0.016	Stabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
D/E	0.2582	likely_benign	0.2694	benign	-0.2	Destabilizing	1.0	D	0.418	neutral	N	0.504405894	None	None	N
D/F	0.8391	likely_pathogenic	0.8514	pathogenic	-0.116	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
D/G	0.3972	ambiguous	0.3967	ambiguous	-0.021	Destabilizing	1.0	D	0.549	neutral	N	0.510725339	None	None	N
D/H	0.6214	likely_pathogenic	0.6102	pathogenic	0.415	Stabilizing	1.0	D	0.645	neutral	D	0.591898832	None	None	N
D/I	0.6822	likely_pathogenic	0.6786	pathogenic	0.248	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
D/K	0.609	likely_pathogenic	0.595	pathogenic	0.478	Stabilizing	1.0	D	0.601	neutral	None	None	None	None	N
D/L	0.6804	likely_pathogenic	0.6776	pathogenic	0.248	Stabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
D/M	0.8304	likely_pathogenic	0.848	pathogenic	0.119	Stabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
D/N	0.2044	likely_benign	0.2112	benign	0.402	Stabilizing	1.0	D	0.589	neutral	N	0.505901564	None	None	N
D/P	0.7061	likely_pathogenic	0.7386	pathogenic	0.208	Stabilizing	1.0	D	0.619	neutral	None	None	None	None	N
D/Q	0.5736	likely_pathogenic	0.5777	pathogenic	0.378	Stabilizing	1.0	D	0.644	neutral	None	None	None	None	N
D/R	0.6575	likely_pathogenic	0.6396	pathogenic	0.631	Stabilizing	1.0	D	0.666	neutral	None	None	None	None	N
D/S	0.295	likely_benign	0.2994	benign	0.264	Stabilizing	1.0	D	0.586	neutral	None	None	None	None	N
D/T	0.5472	ambiguous	0.5688	pathogenic	0.338	Stabilizing	1.0	D	0.603	neutral	None	None	None	None	N
D/V	0.5196	ambiguous	0.507	ambiguous	0.208	Stabilizing	1.0	D	0.707	prob.neutral	D	0.591898832	None	None	N
D/W	0.9462	likely_pathogenic	0.9502	pathogenic	-0.111	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
D/Y	0.5402	ambiguous	0.5187	ambiguous	0.103	Stabilizing	1.0	D	0.701	prob.neutral	D	0.593644374	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.