TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32163	96712;96713;96714	chr2:178543486;178543485;178543484	chr2:179408213;179408212;179408211
N2AB	30522	91789;91790;91791	chr2:178543486;178543485;178543484	chr2:179408213;179408212;179408211
N2A	29595	89008;89009;89010	chr2:178543486;178543485;178543484	chr2:179408213;179408212;179408211
N2B	23098	69517;69518;69519	chr2:178543486;178543485;178543484	chr2:179408213;179408212;179408211
Novex-1	23223	69892;69893;69894	chr2:178543486;178543485;178543484	chr2:179408213;179408212;179408211
Novex-2	23290	70093;70094;70095	chr2:178543486;178543485;178543484	chr2:179408213;179408212;179408211
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-122
• Domain position: 59
• Structural Position: 90
• Q(SASA): 0.1682
• 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/F	rs1448896859	-1.234	0.046	N	0.451	0.109	0.408853032482	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
L/F	rs1448896859	-1.234	0.046	N	0.451	0.109	0.408853032482	gnomAD-4.0.0	1.59147E-06	None	None	None	None	N	None	5.65547E-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
L/A	0.1352	likely_benign	0.1152	benign	-1.787	Destabilizing	0.91	D	0.468	neutral	None	None	None	None	N
L/C	0.3496	ambiguous	0.2911	benign	-0.786	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
L/D	0.7135	likely_pathogenic	0.5961	pathogenic	-1.399	Destabilizing	0.998	D	0.789	deleterious	None	None	None	None	N
L/E	0.4533	ambiguous	0.3544	ambiguous	-1.302	Destabilizing	0.993	D	0.777	deleterious	None	None	None	None	N
L/F	0.093	likely_benign	0.083	benign	-1.068	Destabilizing	0.046	N	0.451	neutral	N	0.445637269	None	None	N
L/G	0.397	ambiguous	0.3193	benign	-2.191	Highly Destabilizing	0.993	D	0.745	deleterious	None	None	None	None	N
L/H	0.1731	likely_benign	0.1324	benign	-1.38	Destabilizing	0.999	D	0.752	deleterious	N	0.431265249	None	None	N
L/I	0.0676	likely_benign	0.0668	benign	-0.7	Destabilizing	0.885	D	0.471	neutral	N	0.439346015	None	None	N
L/K	0.4231	ambiguous	0.3304	benign	-1.18	Destabilizing	0.993	D	0.707	prob.neutral	None	None	None	None	N
L/M	0.0718	likely_benign	0.0718	benign	-0.445	Destabilizing	0.993	D	0.641	neutral	None	None	None	None	N
L/N	0.2211	likely_benign	0.1799	benign	-1.161	Destabilizing	0.998	D	0.784	deleterious	None	None	None	None	N
L/P	0.8991	likely_pathogenic	0.8289	pathogenic	-1.035	Destabilizing	0.997	D	0.784	deleterious	N	0.462068159	None	None	N
L/Q	0.133	likely_benign	0.1106	benign	-1.218	Destabilizing	0.998	D	0.744	deleterious	None	None	None	None	N
L/R	0.3202	likely_benign	0.2388	benign	-0.685	Destabilizing	0.991	D	0.747	deleterious	N	0.398382039	None	None	N
L/S	0.1265	likely_benign	0.101	benign	-1.803	Destabilizing	0.993	D	0.7	prob.neutral	None	None	None	None	N
L/T	0.1014	likely_benign	0.0912	benign	-1.585	Destabilizing	0.986	D	0.619	neutral	None	None	None	None	N
L/V	0.0625	likely_benign	0.0622	benign	-1.035	Destabilizing	0.046	N	0.527	neutral	N	0.466916618	None	None	N
L/W	0.2717	likely_benign	0.2083	benign	-1.287	Destabilizing	0.999	D	0.716	prob.delet.	None	None	None	None	N
L/Y	0.2532	likely_benign	0.2162	benign	-1.006	Destabilizing	0.973	D	0.655	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.