TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24574	73945;73946;73947	chr2:178572412;178572411;178572410	chr2:179437139;179437138;179437137
N2AB	22933	69022;69023;69024	chr2:178572412;178572411;178572410	chr2:179437139;179437138;179437137
N2A	22006	66241;66242;66243	chr2:178572412;178572411;178572410	chr2:179437139;179437138;179437137
N2B	15509	46750;46751;46752	chr2:178572412;178572411;178572410	chr2:179437139;179437138;179437137
Novex-1	15634	47125;47126;47127	chr2:178572412;178572411;178572410	chr2:179437139;179437138;179437137
Novex-2	15701	47326;47327;47328	chr2:178572412;178572411;178572410	chr2:179437139;179437138;179437137
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: Fn3-66
• Domain position: 56
• Structural Position: 83
• Q(SASA): 0.3915
• 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/L	rs754917150	1.178	0.399	N	0.377	0.217	0.368369118721	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	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	0.2243	likely_benign	0.2337	benign	0.453	Stabilizing	0.478	N	0.375	neutral	None	None	None	None	N
H/C	0.141	likely_benign	0.1525	benign	1.022	Stabilizing	0.991	D	0.337	neutral	None	None	None	None	N
H/D	0.3933	ambiguous	0.3998	ambiguous	0.197	Stabilizing	0.501	D	0.41	neutral	N	0.470167567	None	None	N
H/E	0.4204	ambiguous	0.4242	ambiguous	0.223	Stabilizing	0.647	D	0.351	neutral	None	None	None	None	N
H/F	0.2423	likely_benign	0.2588	benign	1.06	Stabilizing	0.946	D	0.372	neutral	None	None	None	None	N
H/G	0.2348	likely_benign	0.2429	benign	0.157	Stabilizing	0.816	D	0.376	neutral	None	None	None	None	N
H/I	0.224	likely_benign	0.248	benign	1.207	Stabilizing	0.861	D	0.354	neutral	None	None	None	None	N
H/K	0.333	likely_benign	0.3513	ambiguous	0.494	Stabilizing	0.638	D	0.41	neutral	None	None	None	None	N
H/L	0.0957	likely_benign	0.1019	benign	1.207	Stabilizing	0.399	N	0.377	neutral	N	0.504394784	None	None	N
H/M	0.3254	likely_benign	0.3488	ambiguous	0.99	Stabilizing	0.993	D	0.339	neutral	None	None	None	None	N
H/N	0.0858	likely_benign	0.0945	benign	0.592	Stabilizing	0.501	D	0.415	neutral	N	0.411753981	None	None	N
H/P	0.0966	likely_benign	0.1002	benign	0.982	Stabilizing	0.001	N	0.171	neutral	N	0.425856642	None	None	N
H/Q	0.1647	likely_benign	0.1748	benign	0.691	Stabilizing	0.908	D	0.39	neutral	N	0.474477308	None	None	N
H/R	0.1842	likely_benign	0.1877	benign	-0.16	Destabilizing	0.823	D	0.367	neutral	N	0.456080762	None	None	N
H/S	0.1542	likely_benign	0.1636	benign	0.688	Stabilizing	0.689	D	0.417	neutral	None	None	None	None	N
H/T	0.1719	likely_benign	0.1904	benign	0.814	Stabilizing	0.004	N	0.257	neutral	None	None	None	None	N
H/V	0.1899	likely_benign	0.2033	benign	0.982	Stabilizing	0.479	N	0.359	neutral	None	None	None	None	N
H/W	0.4026	ambiguous	0.4019	ambiguous	1.027	Stabilizing	0.998	D	0.406	neutral	None	None	None	None	N
H/Y	0.1089	likely_benign	0.1189	benign	1.353	Stabilizing	0.976	D	0.396	neutral	N	0.470025658	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.