TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2344	7255;7256;7257	chr2:178774234;178774233;178774232	chr2:179638961;179638960;179638959
N2AB	2344	7255;7256;7257	chr2:178774234;178774233;178774232	chr2:179638961;179638960;179638959
N2A	2344	7255;7256;7257	chr2:178774234;178774233;178774232	chr2:179638961;179638960;179638959
N2B	2298	7117;7118;7119	chr2:178774234;178774233;178774232	chr2:179638961;179638960;179638959
Novex-1	2298	7117;7118;7119	chr2:178774234;178774233;178774232	chr2:179638961;179638960;179638959
Novex-2	2298	7117;7118;7119	chr2:178774234;178774233;178774232	chr2:179638961;179638960;179638959
Novex-3	2344	7255;7256;7257	chr2:178774234;178774233;178774232	chr2:179638961;179638960;179638959

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-12
• Domain position: 78
• Structural Position: 168
• Q(SASA): 0.3638
• 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
K/R	None	None	0.005	N	0.181	0.054	0.136095386433	gnomAD-4.0.0	1.59062E-06	None	None	None	None	N	None	5.65483E-05	0	None	0	0	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
K/A	0.4362	ambiguous	0.4142	ambiguous	-0.417	Destabilizing	0.688	D	0.506	neutral	None	None	None	None	N
K/C	0.7505	likely_pathogenic	0.7235	pathogenic	-0.572	Destabilizing	0.998	D	0.573	neutral	None	None	None	None	N
K/D	0.7593	likely_pathogenic	0.7287	pathogenic	0.396	Stabilizing	0.915	D	0.543	neutral	None	None	None	None	N
K/E	0.2054	likely_benign	0.1787	benign	0.463	Stabilizing	0.801	D	0.538	neutral	N	0.43917313	None	None	N
K/F	0.8244	likely_pathogenic	0.7976	pathogenic	-0.383	Destabilizing	0.991	D	0.594	neutral	None	None	None	None	N
K/G	0.6267	likely_pathogenic	0.5997	pathogenic	-0.7	Destabilizing	0.915	D	0.555	neutral	None	None	None	None	N
K/H	0.3871	ambiguous	0.3543	ambiguous	-0.936	Destabilizing	0.974	D	0.561	neutral	None	None	None	None	N
K/I	0.3617	ambiguous	0.3207	benign	0.277	Stabilizing	0.949	D	0.617	neutral	None	None	None	None	N
K/L	0.434	ambiguous	0.3958	ambiguous	0.277	Stabilizing	0.842	D	0.565	neutral	None	None	None	None	N
K/M	0.2261	likely_benign	0.1921	benign	0.097	Stabilizing	0.989	D	0.559	neutral	N	0.447652384	None	None	N
K/N	0.4709	ambiguous	0.4357	ambiguous	-0.106	Destabilizing	0.801	D	0.507	neutral	N	0.453122896	None	None	N
K/P	0.9208	likely_pathogenic	0.9217	pathogenic	0.075	Stabilizing	0.991	D	0.579	neutral	None	None	None	None	N
K/Q	0.1454	likely_benign	0.1278	benign	-0.232	Destabilizing	0.801	D	0.537	neutral	N	0.417648176	None	None	N
K/R	0.0979	likely_benign	0.0879	benign	-0.214	Destabilizing	0.005	N	0.181	neutral	N	0.439656767	None	None	N
K/S	0.4576	ambiguous	0.4423	ambiguous	-0.819	Destabilizing	0.728	D	0.531	neutral	None	None	None	None	N
K/T	0.1679	likely_benign	0.1542	benign	-0.561	Destabilizing	0.022	N	0.284	neutral	N	0.426636273	None	None	N
K/V	0.3375	likely_benign	0.3006	benign	0.075	Stabilizing	0.842	D	0.578	neutral	None	None	None	None	N
K/W	0.8408	likely_pathogenic	0.8103	pathogenic	-0.252	Destabilizing	0.998	D	0.605	neutral	None	None	None	None	N
K/Y	0.6729	likely_pathogenic	0.6338	pathogenic	0.066	Stabilizing	0.991	D	0.601	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.