TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32268	97027;97028;97029	chr2:178543171;178543170;178543169	chr2:179407898;179407897;179407896
N2AB	30627	92104;92105;92106	chr2:178543171;178543170;178543169	chr2:179407898;179407897;179407896
N2A	29700	89323;89324;89325	chr2:178543171;178543170;178543169	chr2:179407898;179407897;179407896
N2B	23203	69832;69833;69834	chr2:178543171;178543170;178543169	chr2:179407898;179407897;179407896
Novex-1	23328	70207;70208;70209	chr2:178543171;178543170;178543169	chr2:179407898;179407897;179407896
Novex-2	23395	70408;70409;70410	chr2:178543171;178543170;178543169	chr2:179407898;179407897;179407896
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-123
• Domain position: 67
• Structural Position: 98
• Q(SASA): 0.6024
• 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
N/H	None	None	0.996	N	0.371	0.343	0.283371740733	gnomAD-4.0.0	2.40067E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62503E-06	0	0
N/S	rs769680688	-0.447	0.704	N	0.322	0.119	0.166414681773	gnomAD-2.1.1	2.01E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	4.44E-05	0
N/S	rs769680688	-0.447	0.704	N	0.322	0.119	0.166414681773	gnomAD-4.0.0	2.53185E-05	None	None	None	None	N	None	2.98864E-05	0	None	0	0	None	0	0	3.14855E-05	0	1.65689E-05

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
N/A	0.1967	likely_benign	0.1715	benign	-0.725	Destabilizing	0.863	D	0.377	neutral	None	None	None	None	N
N/C	0.2786	likely_benign	0.2522	benign	0.081	Stabilizing	0.999	D	0.404	neutral	None	None	None	None	N
N/D	0.2507	likely_benign	0.2247	benign	0.212	Stabilizing	0.959	D	0.313	neutral	N	0.487022531	None	None	N
N/E	0.3846	ambiguous	0.3635	ambiguous	0.243	Stabilizing	0.969	D	0.286	neutral	None	None	None	None	N
N/F	0.5586	ambiguous	0.4936	ambiguous	-0.871	Destabilizing	0.982	D	0.431	neutral	None	None	None	None	N
N/G	0.2734	likely_benign	0.241	benign	-0.971	Destabilizing	0.969	D	0.29	neutral	None	None	None	None	N
N/H	0.0911	likely_benign	0.0875	benign	-0.757	Destabilizing	0.996	D	0.371	neutral	N	0.508187237	None	None	N
N/I	0.1989	likely_benign	0.1623	benign	-0.141	Destabilizing	0.852	D	0.413	neutral	N	0.451544521	None	None	N
N/K	0.246	likely_benign	0.2383	benign	0.079	Stabilizing	0.92	D	0.285	neutral	N	0.437361715	None	None	N
N/L	0.1925	likely_benign	0.1675	benign	-0.141	Destabilizing	0.759	D	0.4	neutral	None	None	None	None	N
N/M	0.2885	likely_benign	0.2445	benign	0.174	Stabilizing	0.579	D	0.385	neutral	None	None	None	None	N
N/P	0.5198	ambiguous	0.4658	ambiguous	-0.307	Destabilizing	0.997	D	0.423	neutral	None	None	None	None	N
N/Q	0.2559	likely_benign	0.2415	benign	-0.475	Destabilizing	0.991	D	0.349	neutral	None	None	None	None	N
N/R	0.2469	likely_benign	0.2516	benign	0.113	Stabilizing	0.969	D	0.351	neutral	None	None	None	None	N
N/S	0.0833	likely_benign	0.0785	benign	-0.458	Destabilizing	0.704	D	0.322	neutral	N	0.464588389	None	None	N
N/T	0.1034	likely_benign	0.0942	benign	-0.239	Destabilizing	0.061	N	0.079	neutral	N	0.424395205	None	None	N
N/V	0.1924	likely_benign	0.1624	benign	-0.307	Destabilizing	0.884	D	0.404	neutral	None	None	None	None	N
N/W	0.7089	likely_pathogenic	0.6777	pathogenic	-0.704	Destabilizing	0.999	D	0.461	neutral	None	None	None	None	N
N/Y	0.1835	likely_benign	0.1752	benign	-0.472	Destabilizing	0.996	D	0.421	neutral	N	0.469558359	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.