TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19353	58282;58283;58284	chr2:178594437;178594436;178594435	chr2:179459164;179459163;179459162
N2AB	17712	53359;53360;53361	chr2:178594437;178594436;178594435	chr2:179459164;179459163;179459162
N2A	16785	50578;50579;50580	chr2:178594437;178594436;178594435	chr2:179459164;179459163;179459162
N2B	10288	31087;31088;31089	chr2:178594437;178594436;178594435	chr2:179459164;179459163;179459162
Novex-1	10413	31462;31463;31464	chr2:178594437;178594436;178594435	chr2:179459164;179459163;179459162
Novex-2	10480	31663;31664;31665	chr2:178594437;178594436;178594435	chr2:179459164;179459163;179459162
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: Fn3-28
• Domain position: 70
• Structural Position: 102
• Q(SASA): 0.2384
• 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	None	None	0.978	N	0.49	0.311	0.229924730088	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
D/A	0.2581	likely_benign	0.1798	benign	-0.578	Destabilizing	0.9	D	0.488	neutral	N	0.43293733	None	None	N
D/C	0.7641	likely_pathogenic	0.6551	pathogenic	-0.265	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	N
D/E	0.2301	likely_benign	0.176	benign	-0.707	Destabilizing	0.948	D	0.487	neutral	N	0.413351492	None	None	N
D/F	0.7369	likely_pathogenic	0.6435	pathogenic	-0.055	Destabilizing	0.999	D	0.654	neutral	None	None	None	None	N
D/G	0.347	ambiguous	0.2566	benign	-0.949	Destabilizing	0.978	D	0.446	neutral	N	0.450832445	None	None	N
D/H	0.5087	ambiguous	0.3996	ambiguous	-0.331	Destabilizing	1.0	D	0.509	neutral	N	0.434497555	None	None	N
D/I	0.6264	likely_pathogenic	0.515	ambiguous	0.408	Stabilizing	0.998	D	0.651	neutral	None	None	None	None	N
D/K	0.6198	likely_pathogenic	0.5044	ambiguous	-0.396	Destabilizing	0.983	D	0.538	neutral	None	None	None	None	N
D/L	0.6475	likely_pathogenic	0.5328	ambiguous	0.408	Stabilizing	0.998	D	0.631	neutral	None	None	None	None	N
D/M	0.7017	likely_pathogenic	0.6118	pathogenic	0.846	Stabilizing	1.0	D	0.63	neutral	None	None	None	None	N
D/N	0.1272	likely_benign	0.1069	benign	-0.941	Destabilizing	0.978	D	0.49	neutral	N	0.454083394	None	None	N
D/P	0.9865	likely_pathogenic	0.9795	pathogenic	0.105	Stabilizing	0.998	D	0.54	neutral	None	None	None	None	N
D/Q	0.4597	ambiguous	0.358	ambiguous	-0.765	Destabilizing	0.998	D	0.537	neutral	None	None	None	None	N
D/R	0.7415	likely_pathogenic	0.6227	pathogenic	-0.183	Destabilizing	0.998	D	0.581	neutral	None	None	None	None	N
D/S	0.1768	likely_benign	0.1376	benign	-1.18	Destabilizing	0.487	N	0.145	neutral	None	None	None	None	N
D/T	0.4112	ambiguous	0.3217	benign	-0.867	Destabilizing	0.967	D	0.489	neutral	None	None	None	None	N
D/V	0.4376	ambiguous	0.329	benign	0.105	Stabilizing	0.997	D	0.659	neutral	N	0.419085386	None	None	N
D/W	0.9637	likely_pathogenic	0.9391	pathogenic	0.164	Stabilizing	1.0	D	0.629	neutral	None	None	None	None	N
D/Y	0.405	ambiguous	0.3129	benign	0.196	Stabilizing	0.999	D	0.654	neutral	N	0.472013894	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.