TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26429	79510;79511;79512	chr2:178566847;178566846;178566845	chr2:179431574;179431573;179431572
N2AB	24788	74587;74588;74589	chr2:178566847;178566846;178566845	chr2:179431574;179431573;179431572
N2A	23861	71806;71807;71808	chr2:178566847;178566846;178566845	chr2:179431574;179431573;179431572
N2B	17364	52315;52316;52317	chr2:178566847;178566846;178566845	chr2:179431574;179431573;179431572
Novex-1	17489	52690;52691;52692	chr2:178566847;178566846;178566845	chr2:179431574;179431573;179431572
Novex-2	17556	52891;52892;52893	chr2:178566847;178566846;178566845	chr2:179431574;179431573;179431572
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-80
• Domain position: 44
• Structural Position: 54
• Q(SASA): 0.7606
• 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/N	None	None	0.491	N	0.24	0.092	0.16115917748	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	1.26695E-04	0	None	0	0	None	0	0	0	0	0
S/R	None	None	0.491	N	0.278	0.174	0.216624796971	gnomAD-4.0.0	1.59205E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43283E-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
S/A	0.063	likely_benign	0.055	benign	-0.166	Destabilizing	0.001	N	0.104	neutral	None	None	None	None	I
S/C	0.1138	likely_benign	0.0977	benign	-0.274	Destabilizing	0.873	D	0.215	neutral	N	0.467547351	None	None	I
S/D	0.4586	ambiguous	0.3645	ambiguous	-0.031	Destabilizing	0.002	N	0.096	neutral	None	None	None	None	I
S/E	0.5454	ambiguous	0.4478	ambiguous	-0.139	Destabilizing	0.209	N	0.246	neutral	None	None	None	None	I
S/F	0.2239	likely_benign	0.1654	benign	-0.896	Destabilizing	0.901	D	0.297	neutral	None	None	None	None	I
S/G	0.0804	likely_benign	0.072	benign	-0.218	Destabilizing	0.08	N	0.194	neutral	N	0.407732241	None	None	I
S/H	0.3609	ambiguous	0.3018	benign	-0.544	Destabilizing	0.004	N	0.224	neutral	None	None	None	None	I
S/I	0.1932	likely_benign	0.14	benign	-0.161	Destabilizing	0.491	N	0.296	neutral	N	0.507072516	None	None	I
S/K	0.6624	likely_pathogenic	0.5538	ambiguous	-0.396	Destabilizing	0.345	N	0.199	neutral	None	None	None	None	I
S/L	0.0858	likely_benign	0.071	benign	-0.161	Destabilizing	0.345	N	0.279	neutral	None	None	None	None	I
S/M	0.159	likely_benign	0.1318	benign	-0.116	Destabilizing	0.965	D	0.218	neutral	None	None	None	None	I
S/N	0.1284	likely_benign	0.1034	benign	-0.077	Destabilizing	0.491	N	0.24	neutral	N	0.428376872	None	None	I
S/P	0.4669	ambiguous	0.3912	ambiguous	-0.138	Destabilizing	0.722	D	0.282	neutral	None	None	None	None	I
S/Q	0.4544	ambiguous	0.3856	ambiguous	-0.316	Destabilizing	0.561	D	0.191	neutral	None	None	None	None	I
S/R	0.6228	likely_pathogenic	0.5124	ambiguous	-0.118	Destabilizing	0.491	N	0.278	neutral	N	0.466897975	None	None	I
S/T	0.0751	likely_benign	0.0671	benign	-0.186	Destabilizing	0.285	N	0.32	neutral	N	0.443906472	None	None	I
S/V	0.1731	likely_benign	0.1318	benign	-0.138	Destabilizing	0.39	N	0.28	neutral	None	None	None	None	I
S/W	0.3887	ambiguous	0.3199	benign	-0.986	Destabilizing	0.991	D	0.283	neutral	None	None	None	None	I
S/Y	0.233	likely_benign	0.168	benign	-0.672	Destabilizing	0.692	D	0.309	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.