TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22581	67966;67967;67968	chr2:178579289;178579288;178579287	chr2:179444016;179444015;179444014
N2AB	20940	63043;63044;63045	chr2:178579289;178579288;178579287	chr2:179444016;179444015;179444014
N2A	20013	60262;60263;60264	chr2:178579289;178579288;178579287	chr2:179444016;179444015;179444014
N2B	13516	40771;40772;40773	chr2:178579289;178579288;178579287	chr2:179444016;179444015;179444014
Novex-1	13641	41146;41147;41148	chr2:178579289;178579288;178579287	chr2:179444016;179444015;179444014
Novex-2	13708	41347;41348;41349	chr2:178579289;178579288;178579287	chr2:179444016;179444015;179444014
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-127
• Domain position: 22
• Structural Position: 45
• Q(SASA): 0.3385
• Predicted PPI site: I

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
S/T	rs1318211232	None	0.001	N	0.163	0.073	0.104622674875	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
S/T	rs1318211232	None	0.001	N	0.163	0.073	0.104622674875	gnomAD-4.0.0	5.12877E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.579E-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
S/A	0.0638	likely_benign	0.063	benign	-0.367	Destabilizing	0.002	N	0.175	neutral	N	0.442440327	None	None	I
S/C	0.0993	likely_benign	0.1005	benign	-0.332	Destabilizing	0.977	D	0.365	neutral	None	None	None	None	I
S/D	0.3239	likely_benign	0.3114	benign	0.072	Stabilizing	0.617	D	0.3	neutral	None	None	None	None	I
S/E	0.323	likely_benign	0.3055	benign	-0.003	Destabilizing	0.617	D	0.281	neutral	None	None	None	None	I
S/F	0.1372	likely_benign	0.1293	benign	-0.861	Destabilizing	0.92	D	0.473	neutral	None	None	None	None	I
S/G	0.1	likely_benign	0.1024	benign	-0.515	Destabilizing	0.25	N	0.313	neutral	None	None	None	None	I
S/H	0.2486	likely_benign	0.2488	benign	-1.026	Destabilizing	0.992	D	0.363	neutral	None	None	None	None	I
S/I	0.0899	likely_benign	0.0848	benign	-0.106	Destabilizing	0.85	D	0.444	neutral	None	None	None	None	I
S/K	0.4081	ambiguous	0.3912	ambiguous	-0.599	Destabilizing	0.617	D	0.277	neutral	None	None	None	None	I
S/L	0.0692	likely_benign	0.0681	benign	-0.106	Destabilizing	0.379	N	0.41	neutral	N	0.478689128	None	None	I
S/M	0.1201	likely_benign	0.119	benign	0.048	Stabilizing	0.92	D	0.371	neutral	None	None	None	None	I
S/N	0.1199	likely_benign	0.1191	benign	-0.364	Destabilizing	0.617	D	0.363	neutral	None	None	None	None	I
S/P	0.6629	likely_pathogenic	0.6139	pathogenic	-0.162	Destabilizing	0.896	D	0.397	neutral	N	0.516476726	None	None	I
S/Q	0.3055	likely_benign	0.3012	benign	-0.565	Destabilizing	0.92	D	0.377	neutral	None	None	None	None	I
S/R	0.3625	ambiguous	0.3478	ambiguous	-0.414	Destabilizing	0.85	D	0.399	neutral	None	None	None	None	I
S/T	0.0544	likely_benign	0.0542	benign	-0.421	Destabilizing	0.001	N	0.163	neutral	N	0.397937401	None	None	I
S/V	0.0867	likely_benign	0.083	benign	-0.162	Destabilizing	0.447	N	0.409	neutral	None	None	None	None	I
S/W	0.3224	likely_benign	0.3183	benign	-0.89	Destabilizing	0.992	D	0.537	neutral	None	None	None	None	I
S/Y	0.1727	likely_benign	0.1654	benign	-0.609	Destabilizing	0.972	D	0.469	neutral	None	None	None	None	I

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.