TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34326	103201;103202;103203	chr2:178533639;178533638;178533637	chr2:179398366;179398365;179398364
N2AB	32685	98278;98279;98280	chr2:178533639;178533638;178533637	chr2:179398366;179398365;179398364
N2A	31758	95497;95498;95499	chr2:178533639;178533638;178533637	chr2:179398366;179398365;179398364
N2B	25261	76006;76007;76008	chr2:178533639;178533638;178533637	chr2:179398366;179398365;179398364
Novex-1	25386	76381;76382;76383	chr2:178533639;178533638;178533637	chr2:179398366;179398365;179398364
Novex-2	25453	76582;76583;76584	chr2:178533639;178533638;178533637	chr2:179398366;179398365;179398364
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-161
• Domain position: 69
• Structural Position: 148
• Q(SASA): 0.5875
• 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
D/N	rs1227502652	None	0.004	N	0.224	0.127	0.134241683229	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
D/N	rs1227502652	None	0.004	N	0.224	0.127	0.134241683229	gnomAD-4.0.0	6.56935E-06	None	None	None	None	N	None	2.41208E-05	0	None	0	0	None	0	0	0	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
D/A	0.1034	likely_benign	0.1028	benign	-0.193	Destabilizing	0.062	N	0.409	neutral	N	0.437320777	None	None	N
D/C	0.5624	ambiguous	0.5745	pathogenic	0.253	Stabilizing	0.935	D	0.535	neutral	None	None	None	None	N
D/E	0.0889	likely_benign	0.0881	benign	-0.236	Destabilizing	None	N	0.145	neutral	N	0.387811889	None	None	N
D/F	0.5744	likely_pathogenic	0.5815	pathogenic	-0.371	Destabilizing	0.791	D	0.481	neutral	None	None	None	None	N
D/G	0.1283	likely_benign	0.1296	benign	-0.331	Destabilizing	None	N	0.232	neutral	N	0.482285062	None	None	N
D/H	0.2441	likely_benign	0.2419	benign	-0.132	Destabilizing	0.484	N	0.416	neutral	N	0.438000754	None	None	N
D/I	0.3202	likely_benign	0.3203	benign	0.109	Stabilizing	0.555	D	0.479	neutral	None	None	None	None	N
D/K	0.2274	likely_benign	0.2088	benign	0.512	Stabilizing	0.081	N	0.386	neutral	None	None	None	None	N
D/L	0.3183	likely_benign	0.3086	benign	0.109	Stabilizing	0.38	N	0.449	neutral	None	None	None	None	N
D/M	0.4904	ambiguous	0.4828	ambiguous	0.298	Stabilizing	0.935	D	0.474	neutral	None	None	None	None	N
D/N	0.0913	likely_benign	0.0982	benign	0.334	Stabilizing	0.004	N	0.224	neutral	N	0.47133735	None	None	N
D/P	0.7269	likely_pathogenic	0.6861	pathogenic	0.029	Stabilizing	0.555	D	0.407	neutral	None	None	None	None	N
D/Q	0.2257	likely_benign	0.2119	benign	0.327	Stabilizing	0.235	N	0.385	neutral	None	None	None	None	N
D/R	0.2887	likely_benign	0.2648	benign	0.572	Stabilizing	0.235	N	0.467	neutral	None	None	None	None	N
D/S	0.0868	likely_benign	0.0898	benign	0.236	Stabilizing	0.007	N	0.231	neutral	None	None	None	None	N
D/T	0.1633	likely_benign	0.1653	benign	0.341	Stabilizing	0.081	N	0.385	neutral	None	None	None	None	N
D/V	0.1924	likely_benign	0.1937	benign	0.029	Stabilizing	0.317	N	0.458	neutral	N	0.440393837	None	None	N
D/W	0.8393	likely_pathogenic	0.8228	pathogenic	-0.319	Destabilizing	0.935	D	0.609	neutral	None	None	None	None	N
D/Y	0.2473	likely_benign	0.2527	benign	-0.149	Destabilizing	0.741	D	0.48	neutral	N	0.438254244	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.