TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35719	107380;107381;107382	chr2:178528596;178528595;178528594	chr2:179393323;179393322;179393321
N2AB	34078	102457;102458;102459	chr2:178528596;178528595;178528594	chr2:179393323;179393322;179393321
N2A	33151	99676;99677;99678	chr2:178528596;178528595;178528594	chr2:179393323;179393322;179393321
N2B	26654	80185;80186;80187	chr2:178528596;178528595;178528594	chr2:179393323;179393322;179393321
Novex-1	26779	80560;80561;80562	chr2:178528596;178528595;178528594	chr2:179393323;179393322;179393321
Novex-2	26846	80761;80762;80763	chr2:178528596;178528595;178528594	chr2:179393323;179393322;179393321
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-168
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.1279
• 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
V/A	None	None	0.002	N	0.305	0.209	0.370051654043	gnomAD-4.0.0	1.59318E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86103E-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
V/A	0.321	likely_benign	0.2975	benign	-2.117	Highly Destabilizing	0.002	N	0.305	neutral	N	0.395008086	None	None	N
V/C	0.8985	likely_pathogenic	0.8984	pathogenic	-1.607	Destabilizing	0.947	D	0.784	deleterious	None	None	None	None	N
V/D	0.9641	likely_pathogenic	0.9677	pathogenic	-2.518	Highly Destabilizing	0.638	D	0.814	deleterious	N	0.50707618	None	None	N
V/E	0.9325	likely_pathogenic	0.9419	pathogenic	-2.305	Highly Destabilizing	0.7	D	0.766	deleterious	None	None	None	None	N
V/F	0.6736	likely_pathogenic	0.6862	pathogenic	-1.299	Destabilizing	0.781	D	0.796	deleterious	N	0.461117526	None	None	N
V/G	0.6577	likely_pathogenic	0.6517	pathogenic	-2.652	Highly Destabilizing	0.468	N	0.743	deleterious	N	0.467233592	None	None	N
V/H	0.9774	likely_pathogenic	0.9799	pathogenic	-2.244	Highly Destabilizing	0.982	D	0.825	deleterious	None	None	None	None	N
V/I	0.1076	likely_benign	0.111	benign	-0.627	Destabilizing	0.172	N	0.526	neutral	N	0.465350819	None	None	N
V/K	0.9507	likely_pathogenic	0.9588	pathogenic	-1.893	Destabilizing	0.7	D	0.776	deleterious	None	None	None	None	N
V/L	0.5197	ambiguous	0.5546	ambiguous	-0.627	Destabilizing	0.094	N	0.545	neutral	N	0.48093356	None	None	N
V/M	0.4322	ambiguous	0.4607	ambiguous	-0.567	Destabilizing	0.826	D	0.709	prob.delet.	None	None	None	None	N
V/N	0.9118	likely_pathogenic	0.9202	pathogenic	-2.18	Highly Destabilizing	0.826	D	0.831	deleterious	None	None	None	None	N
V/P	0.984	likely_pathogenic	0.9849	pathogenic	-1.096	Destabilizing	0.7	D	0.794	deleterious	None	None	None	None	N
V/Q	0.9266	likely_pathogenic	0.9333	pathogenic	-2.042	Highly Destabilizing	0.826	D	0.808	deleterious	None	None	None	None	N
V/R	0.9249	likely_pathogenic	0.935	pathogenic	-1.649	Destabilizing	0.7	D	0.823	deleterious	None	None	None	None	N
V/S	0.6561	likely_pathogenic	0.6612	pathogenic	-2.825	Highly Destabilizing	0.539	D	0.739	prob.delet.	None	None	None	None	N
V/T	0.472	ambiguous	0.4827	ambiguous	-2.458	Highly Destabilizing	0.25	N	0.596	neutral	None	None	None	None	N
V/W	0.9919	likely_pathogenic	0.9939	pathogenic	-1.75	Destabilizing	0.982	D	0.803	deleterious	None	None	None	None	N
V/Y	0.9566	likely_pathogenic	0.9583	pathogenic	-1.375	Destabilizing	0.826	D	0.807	deleterious	None	None	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.