TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18773	56542;56543;56544	chr2:178599584;178599583;178599582	chr2:179464311;179464310;179464309
N2AB	17132	51619;51620;51621	chr2:178599584;178599583;178599582	chr2:179464311;179464310;179464309
N2A	16205	48838;48839;48840	chr2:178599584;178599583;178599582	chr2:179464311;179464310;179464309
N2B	9708	29347;29348;29349	chr2:178599584;178599583;178599582	chr2:179464311;179464310;179464309
Novex-1	9833	29722;29723;29724	chr2:178599584;178599583;178599582	chr2:179464311;179464310;179464309
Novex-2	9900	29923;29924;29925	chr2:178599584;178599583;178599582	chr2:179464311;179464310;179464309
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-116
• Domain position: 86
• Structural Position: 166
• Q(SASA): 0.4688
• 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
A/T	None	None	0.939	N	0.549	0.414	0.444807159249	gnomAD-4.0.0	1.64746E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.5223E-05	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
A/C	0.4757	ambiguous	0.4352	ambiguous	-0.846	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	I
A/D	0.2317	likely_benign	0.1551	benign	-0.404	Destabilizing	0.128	N	0.461	neutral	None	None	None	None	I
A/E	0.3109	likely_benign	0.2352	benign	-0.548	Destabilizing	0.885	D	0.592	neutral	N	0.520957039	None	None	I
A/F	0.4765	ambiguous	0.4047	ambiguous	-0.9	Destabilizing	0.993	D	0.771	deleterious	None	None	None	None	I
A/G	0.261	likely_benign	0.21	benign	-0.394	Destabilizing	0.939	D	0.515	neutral	N	0.513284147	None	None	I
A/H	0.5645	likely_pathogenic	0.4745	ambiguous	-0.414	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	I
A/I	0.2211	likely_benign	0.2	benign	-0.371	Destabilizing	0.91	D	0.595	neutral	None	None	None	None	I
A/K	0.5504	ambiguous	0.4556	ambiguous	-0.662	Destabilizing	0.986	D	0.605	neutral	None	None	None	None	I
A/L	0.2784	likely_benign	0.2406	benign	-0.371	Destabilizing	0.91	D	0.549	neutral	None	None	None	None	I
A/M	0.281	likely_benign	0.2565	benign	-0.455	Destabilizing	0.998	D	0.661	neutral	None	None	None	None	I
A/N	0.3065	likely_benign	0.2342	benign	-0.401	Destabilizing	0.973	D	0.759	deleterious	None	None	None	None	I
A/P	0.9769	likely_pathogenic	0.9469	pathogenic	-0.325	Destabilizing	0.991	D	0.67	neutral	N	0.495597966	None	None	I
A/Q	0.4094	ambiguous	0.3403	ambiguous	-0.656	Destabilizing	0.993	D	0.666	neutral	None	None	None	None	I
A/R	0.5417	ambiguous	0.4404	ambiguous	-0.223	Destabilizing	0.993	D	0.661	neutral	None	None	None	None	I
A/S	0.105	likely_benign	0.093	benign	-0.616	Destabilizing	0.939	D	0.525	neutral	N	0.507739812	None	None	I
A/T	0.0818	likely_benign	0.0761	benign	-0.675	Destabilizing	0.939	D	0.549	neutral	N	0.519476958	None	None	I
A/V	0.1085	likely_benign	0.103	benign	-0.325	Destabilizing	0.17	N	0.263	neutral	N	0.458580428	None	None	I
A/W	0.8929	likely_pathogenic	0.8361	pathogenic	-1.042	Destabilizing	0.999	D	0.752	deleterious	None	None	None	None	I
A/Y	0.6041	likely_pathogenic	0.4991	ambiguous	-0.693	Destabilizing	0.998	D	0.77	deleterious	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.