TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5032	15319;15320;15321	chr2:178734830;178734829;178734828	chr2:179599557;179599556;179599555
N2AB	4715	14368;14369;14370	chr2:178734830;178734829;178734828	chr2:179599557;179599556;179599555
N2A	3788	11587;11588;11589	chr2:178734830;178734829;178734828	chr2:179599557;179599556;179599555
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-33
• Domain position: 52
• Structural Position: 127
• Q(SASA): 0.2717
• 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
F/C	None	None	1.0	D	0.797	0.566	0.868209140578	gnomAD-4.0.0	1.59135E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8584E-06	0	0
F/L	None	None	0.217	N	0.373	0.298	0.55973633643	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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
F/A	0.7454	likely_pathogenic	0.7134	pathogenic	-1.708	Destabilizing	0.996	D	0.726	prob.delet.	None	None	None	None	N
F/C	0.6651	likely_pathogenic	0.5854	pathogenic	-0.96	Destabilizing	1.0	D	0.797	deleterious	D	0.600793484	None	None	N
F/D	0.9334	likely_pathogenic	0.9263	pathogenic	0.208	Stabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
F/E	0.9434	likely_pathogenic	0.9346	pathogenic	0.27	Stabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
F/G	0.904	likely_pathogenic	0.897	pathogenic	-2.007	Highly Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
F/H	0.7632	likely_pathogenic	0.729	pathogenic	-0.347	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
F/I	0.3926	ambiguous	0.3365	benign	-0.852	Destabilizing	0.978	D	0.648	neutral	N	0.505160246	None	None	N
F/K	0.9457	likely_pathogenic	0.9295	pathogenic	-0.85	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
F/L	0.8833	likely_pathogenic	0.851	pathogenic	-0.852	Destabilizing	0.217	N	0.373	neutral	N	0.508768463	None	None	N
F/M	0.661	likely_pathogenic	0.6256	pathogenic	-0.719	Destabilizing	0.998	D	0.755	deleterious	None	None	None	None	N
F/N	0.8621	likely_pathogenic	0.8361	pathogenic	-0.871	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
F/P	0.9927	likely_pathogenic	0.9911	pathogenic	-1.125	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
F/Q	0.8972	likely_pathogenic	0.884	pathogenic	-0.878	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
F/R	0.8685	likely_pathogenic	0.8369	pathogenic	-0.313	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
F/S	0.6311	likely_pathogenic	0.5971	pathogenic	-1.712	Destabilizing	0.999	D	0.781	deleterious	N	0.507653416	None	None	N
F/T	0.667	likely_pathogenic	0.6327	pathogenic	-1.556	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
F/V	0.3666	ambiguous	0.31	benign	-1.125	Destabilizing	0.978	D	0.659	neutral	N	0.505063751	None	None	N
F/W	0.6727	likely_pathogenic	0.6619	pathogenic	-0.132	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
F/Y	0.2734	likely_benign	0.2496	benign	-0.315	Destabilizing	0.998	D	0.634	neutral	N	0.504546771	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.