TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23588	70987;70988;70989	chr2:178575370;178575369;178575368	chr2:179440097;179440096;179440095
N2AB	21947	66064;66065;66066	chr2:178575370;178575369;178575368	chr2:179440097;179440096;179440095
N2A	21020	63283;63284;63285	chr2:178575370;178575369;178575368	chr2:179440097;179440096;179440095
N2B	14523	43792;43793;43794	chr2:178575370;178575369;178575368	chr2:179440097;179440096;179440095
Novex-1	14648	44167;44168;44169	chr2:178575370;178575369;178575368	chr2:179440097;179440096;179440095
Novex-2	14715	44368;44369;44370	chr2:178575370;178575369;178575368	chr2:179440097;179440096;179440095
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Fn3-59
• Domain position: 57
• Structural Position: 89
• Q(SASA): 0.2648
• 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
L/S	None	None	1.0	N	0.761	0.531	0.675944014053	gnomAD-4.0.0	4.79008E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39724E-06	0	1.65684E-05

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
L/A	0.3488	ambiguous	0.3474	ambiguous	-1.717	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	N
L/C	0.5538	ambiguous	0.5901	pathogenic	-0.908	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
L/D	0.8507	likely_pathogenic	0.8528	pathogenic	-1.634	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
L/E	0.5458	ambiguous	0.5404	ambiguous	-1.483	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
L/F	0.2839	likely_benign	0.3134	benign	-0.99	Destabilizing	1.0	D	0.725	prob.delet.	N	0.470647996	None	None	N
L/G	0.6101	likely_pathogenic	0.6221	pathogenic	-2.143	Highly Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
L/H	0.459	ambiguous	0.4771	ambiguous	-1.321	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
L/I	0.214	likely_benign	0.2035	benign	-0.54	Destabilizing	0.999	D	0.431	neutral	N	0.468735438	None	None	N
L/K	0.4389	ambiguous	0.456	ambiguous	-1.146	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
L/M	0.1114	likely_benign	0.1193	benign	-0.473	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
L/N	0.4388	ambiguous	0.458	ambiguous	-1.354	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
L/P	0.2373	likely_benign	0.2722	benign	-0.908	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
L/Q	0.2289	likely_benign	0.2422	benign	-1.33	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
L/R	0.3714	ambiguous	0.3823	ambiguous	-0.783	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
L/S	0.3964	ambiguous	0.3951	ambiguous	-1.971	Destabilizing	1.0	D	0.761	deleterious	N	0.521884466	None	None	N
L/T	0.1824	likely_benign	0.1821	benign	-1.686	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
L/V	0.176	likely_benign	0.1737	benign	-0.908	Destabilizing	0.999	D	0.475	neutral	N	0.516286646	None	None	N
L/W	0.4846	ambiguous	0.4925	ambiguous	-1.24	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
L/Y	0.6102	likely_pathogenic	0.6408	pathogenic	-0.902	Destabilizing	1.0	D	0.802	deleterious	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.