TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26613	80062;80063;80064	chr2:178566295;178566294;178566293	chr2:179431022;179431021;179431020
N2AB	24972	75139;75140;75141	chr2:178566295;178566294;178566293	chr2:179431022;179431021;179431020
N2A	24045	72358;72359;72360	chr2:178566295;178566294;178566293	chr2:179431022;179431021;179431020
N2B	17548	52867;52868;52869	chr2:178566295;178566294;178566293	chr2:179431022;179431021;179431020
Novex-1	17673	53242;53243;53244	chr2:178566295;178566294;178566293	chr2:179431022;179431021;179431020
Novex-2	17740	53443;53444;53445	chr2:178566295;178566294;178566293	chr2:179431022;179431021;179431020
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-138
• Domain position: 20
• Structural Position: 31
• Q(SASA): 0.3809
• 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
H/Y	rs1276864550	1.14	0.013	N	0.162	0.135	0.235038932564	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
H/Y	rs1276864550	1.14	0.013	N	0.162	0.135	0.235038932564	gnomAD-4.0.0	1.5915E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85876E-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
H/A	0.3219	likely_benign	0.3184	benign	-0.584	Destabilizing	0.103	N	0.389	neutral	None	None	None	None	N
H/C	0.1883	likely_benign	0.181	benign	0.191	Stabilizing	0.002	N	0.367	neutral	None	None	None	None	N
H/D	0.4041	ambiguous	0.3593	ambiguous	-0.685	Destabilizing	0.166	N	0.412	neutral	N	0.426139936	None	None	N
H/E	0.4905	ambiguous	0.445	ambiguous	-0.575	Destabilizing	0.345	N	0.304	neutral	None	None	None	None	N
H/F	0.222	likely_benign	0.2248	benign	0.804	Stabilizing	0.39	N	0.494	neutral	None	None	None	None	N
H/G	0.4423	ambiguous	0.4476	ambiguous	-0.964	Destabilizing	0.209	N	0.41	neutral	None	None	None	None	N
H/I	0.2514	likely_benign	0.2525	benign	0.47	Stabilizing	0.722	D	0.548	neutral	None	None	None	None	N
H/K	0.4626	ambiguous	0.4141	ambiguous	-0.441	Destabilizing	0.345	N	0.415	neutral	None	None	None	None	N
H/L	0.1219	likely_benign	0.12	benign	0.47	Stabilizing	0.285	N	0.431	neutral	N	0.43589557	None	None	N
H/M	0.4007	ambiguous	0.4125	ambiguous	0.238	Stabilizing	0.965	D	0.518	neutral	None	None	None	None	N
H/N	0.1196	likely_benign	0.1155	benign	-0.689	Destabilizing	0.001	N	0.163	neutral	N	0.398241259	None	None	N
H/P	0.3638	ambiguous	0.3542	ambiguous	0.139	Stabilizing	0.662	D	0.589	neutral	N	0.432297904	None	None	N
H/Q	0.2398	likely_benign	0.2283	benign	-0.424	Destabilizing	0.491	N	0.393	neutral	N	0.437645009	None	None	N
H/R	0.2047	likely_benign	0.1825	benign	-1.057	Destabilizing	0.491	N	0.316	neutral	N	0.435375495	None	None	N
H/S	0.2366	likely_benign	0.2303	benign	-0.601	Destabilizing	0.007	N	0.234	neutral	None	None	None	None	N
H/T	0.2663	likely_benign	0.2581	benign	-0.379	Destabilizing	0.209	N	0.43	neutral	None	None	None	None	N
H/V	0.2151	likely_benign	0.2227	benign	0.139	Stabilizing	0.561	D	0.497	neutral	None	None	None	None	N
H/W	0.4212	ambiguous	0.4099	ambiguous	1.108	Stabilizing	0.991	D	0.515	neutral	None	None	None	None	N
H/Y	0.0918	likely_benign	0.0895	benign	1.125	Stabilizing	0.013	N	0.162	neutral	N	0.410557195	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.