TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18837	56734;56735;56736	chr2:178599284;178599283;178599282	chr2:179464011;179464010;179464009
N2AB	17196	51811;51812;51813	chr2:178599284;178599283;178599282	chr2:179464011;179464010;179464009
N2A	16269	49030;49031;49032	chr2:178599284;178599283;178599282	chr2:179464011;179464010;179464009
N2B	9772	29539;29540;29541	chr2:178599284;178599283;178599282	chr2:179464011;179464010;179464009
Novex-1	9897	29914;29915;29916	chr2:178599284;178599283;178599282	chr2:179464011;179464010;179464009
Novex-2	9964	30115;30116;30117	chr2:178599284;178599283;178599282	chr2:179464011;179464010;179464009
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: Fn3-24
• Domain position: 54
• Structural Position: 70
• Q(SASA): 0.6344
• 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
S/G	None	None	0.09	N	0.263	0.076	0.18995819373	gnomAD-4.0.0	1.37886E-06	None	None	None	None	N	None	3.04488E-05	0	None	0	0	None	0	0	0	1.19654E-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	0.0852	likely_benign	0.0866	benign	-0.537	Destabilizing	0.207	N	0.295	neutral	None	None	None	None	N
S/C	0.1227	likely_benign	0.113	benign	-0.41	Destabilizing	0.975	D	0.358	neutral	N	0.505526606	None	None	N
S/D	0.3082	likely_benign	0.2506	benign	-0.735	Destabilizing	0.001	N	0.088	neutral	None	None	None	None	N
S/E	0.4403	ambiguous	0.3718	ambiguous	-0.743	Destabilizing	0.116	N	0.274	neutral	None	None	None	None	N
S/F	0.2831	likely_benign	0.2671	benign	-0.706	Destabilizing	0.932	D	0.355	neutral	None	None	None	None	N
S/G	0.0926	likely_benign	0.0848	benign	-0.791	Destabilizing	0.09	N	0.263	neutral	N	0.501549267	None	None	N
S/H	0.3295	likely_benign	0.2771	benign	-1.375	Destabilizing	0.69	D	0.364	neutral	None	None	None	None	N
S/I	0.2145	likely_benign	0.1943	benign	0.027	Stabilizing	0.773	D	0.388	neutral	N	0.52013224	None	None	N
S/K	0.5324	ambiguous	0.4233	ambiguous	-0.926	Destabilizing	0.002	N	0.129	neutral	None	None	None	None	N
S/L	0.1311	likely_benign	0.1248	benign	0.027	Stabilizing	0.388	N	0.339	neutral	None	None	None	None	N
S/M	0.2286	likely_benign	0.22	benign	0.37	Stabilizing	0.981	D	0.353	neutral	None	None	None	None	N
S/N	0.117	likely_benign	0.1024	benign	-0.902	Destabilizing	None	N	0.08	neutral	N	0.513881059	None	None	N
S/P	0.2201	likely_benign	0.2117	benign	-0.126	Destabilizing	0.818	D	0.401	neutral	None	None	None	None	N
S/Q	0.4349	ambiguous	0.3776	ambiguous	-1.057	Destabilizing	0.388	N	0.325	neutral	None	None	None	None	N
S/R	0.4845	ambiguous	0.3812	ambiguous	-0.785	Destabilizing	0.193	N	0.383	neutral	N	0.494313863	None	None	N
S/T	0.0885	likely_benign	0.0898	benign	-0.815	Destabilizing	0.165	N	0.259	neutral	N	0.475189384	None	None	N
S/V	0.1953	likely_benign	0.1865	benign	-0.126	Destabilizing	0.563	D	0.347	neutral	None	None	None	None	N
S/W	0.3769	ambiguous	0.3322	benign	-0.759	Destabilizing	0.981	D	0.524	neutral	None	None	None	None	N
S/Y	0.2475	likely_benign	0.2095	benign	-0.487	Destabilizing	0.932	D	0.355	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.