TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24291	73096;73097;73098	chr2:178573261;178573260;178573259	chr2:179437988;179437987;179437986
N2AB	22650	68173;68174;68175	chr2:178573261;178573260;178573259	chr2:179437988;179437987;179437986
N2A	21723	65392;65393;65394	chr2:178573261;178573260;178573259	chr2:179437988;179437987;179437986
N2B	15226	45901;45902;45903	chr2:178573261;178573260;178573259	chr2:179437988;179437987;179437986
Novex-1	15351	46276;46277;46278	chr2:178573261;178573260;178573259	chr2:179437988;179437987;179437986
Novex-2	15418	46477;46478;46479	chr2:178573261;178573260;178573259	chr2:179437988;179437987;179437986
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-64
• Domain position: 70
• Structural Position: 102
• Q(SASA): 0.629
• 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/R	None	None	0.942	N	0.489	0.351	0.213573922156	gnomAD-4.0.0	2.06386E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.70918E-06	0	0
H/Y	None	None	0.966	N	0.523	0.521	0.33110744837	gnomAD-4.0.0	1.61157E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.89534E-06	0	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	0.7511	likely_pathogenic	0.657	pathogenic	-0.288	Destabilizing	0.86	D	0.497	neutral	None	None	None	None	N
H/C	0.2444	likely_benign	0.2182	benign	0.704	Stabilizing	0.998	D	0.647	neutral	None	None	None	None	N
H/D	0.7463	likely_pathogenic	0.6343	pathogenic	-0.266	Destabilizing	0.698	D	0.503	neutral	N	0.484913909	None	None	N
H/E	0.7599	likely_pathogenic	0.6708	pathogenic	-0.185	Destabilizing	0.86	D	0.447	neutral	None	None	None	None	N
H/F	0.6358	likely_pathogenic	0.5453	ambiguous	0.785	Stabilizing	0.993	D	0.51	neutral	None	None	None	None	N
H/G	0.7159	likely_pathogenic	0.6029	pathogenic	-0.648	Destabilizing	0.754	D	0.469	neutral	None	None	None	None	N
H/I	0.7454	likely_pathogenic	0.6668	pathogenic	0.691	Stabilizing	0.978	D	0.612	neutral	None	None	None	None	N
H/K	0.4827	ambiguous	0.4361	ambiguous	-0.053	Destabilizing	0.86	D	0.517	neutral	None	None	None	None	N
H/L	0.3911	ambiguous	0.3197	benign	0.691	Stabilizing	0.97	D	0.529	neutral	N	0.467455336	None	None	N
H/M	0.7638	likely_pathogenic	0.7037	pathogenic	0.597	Stabilizing	0.998	D	0.572	neutral	None	None	None	None	N
H/N	0.2937	likely_benign	0.2347	benign	-0.026	Destabilizing	0.014	N	0.138	neutral	N	0.465935183	None	None	N
H/P	0.8992	likely_pathogenic	0.8469	pathogenic	0.387	Stabilizing	0.99	D	0.592	neutral	N	0.508298083	None	None	N
H/Q	0.4422	ambiguous	0.3811	ambiguous	0.197	Stabilizing	0.942	D	0.503	neutral	N	0.498546247	None	None	N
H/R	0.1906	likely_benign	0.171	benign	-0.731	Destabilizing	0.942	D	0.489	neutral	N	0.489617332	None	None	N
H/S	0.6035	likely_pathogenic	0.5041	ambiguous	0.059	Stabilizing	0.754	D	0.458	neutral	None	None	None	None	N
H/T	0.7035	likely_pathogenic	0.6149	pathogenic	0.238	Stabilizing	0.956	D	0.481	neutral	None	None	None	None	N
H/V	0.6693	likely_pathogenic	0.5945	pathogenic	0.387	Stabilizing	0.978	D	0.599	neutral	None	None	None	None	N
H/W	0.6703	likely_pathogenic	0.6093	pathogenic	0.929	Stabilizing	0.998	D	0.647	neutral	None	None	None	None	N
H/Y	0.2745	likely_benign	0.2211	benign	1.093	Stabilizing	0.966	D	0.523	neutral	N	0.497195267	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.