TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4643	14152;14153;14154	chr2:178739306;178739305;178739304	chr2:179604033;179604032;179604031
N2AB	4326	13201;13202;13203	chr2:178739306;178739305;178739304	chr2:179604033;179604032;179604031
N2A	None	None	chr2:None	chr2:None
N2B	4280	13063;13064;13065	chr2:178739306;178739305;178739304	chr2:179604033;179604032;179604031
Novex-1	4405	13438;13439;13440	chr2:178739306;178739305;178739304	chr2:179604033;179604032;179604031
Novex-2	4472	13639;13640;13641	chr2:178739306;178739305;178739304	chr2:179604033;179604032;179604031
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-29
• Domain position: 38
• Structural Position: 56
• Q(SASA): 0.4372
• 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
L/Q	None	None	1.0	N	0.732	0.181	None	gnomAD-4.0.0	1.59208E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85958E-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
L/A	0.1189	likely_benign	0.1221	benign	-1.245	Destabilizing	0.994	D	0.581	neutral	None	None	None	None	N
L/C	0.32	likely_benign	0.3092	benign	-0.706	Destabilizing	0.727	D	0.428	neutral	None	None	None	None	N
L/D	0.4208	ambiguous	0.4868	ambiguous	-0.72	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
L/E	0.1688	likely_benign	0.1842	benign	-0.723	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
L/F	0.1473	likely_benign	0.1568	benign	-0.819	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
L/G	0.342	ambiguous	0.3907	ambiguous	-1.529	Destabilizing	0.999	D	0.754	deleterious	None	None	None	None	N
L/H	0.1516	likely_benign	0.1626	benign	-0.68	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
L/I	0.0811	likely_benign	0.0802	benign	-0.557	Destabilizing	0.994	D	0.493	neutral	None	None	None	None	N
L/K	0.1221	likely_benign	0.1235	benign	-0.864	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
L/M	0.0953	likely_benign	0.0924	benign	-0.515	Destabilizing	1.0	D	0.649	neutral	D	0.614940894	None	None	N
L/N	0.2406	likely_benign	0.2731	benign	-0.733	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
L/P	0.1096	likely_benign	0.1073	benign	-0.754	Destabilizing	1.0	D	0.758	deleterious	N	0.50487581	None	None	N
L/Q	0.0942	likely_benign	0.1008	benign	-0.882	Destabilizing	1.0	D	0.732	prob.delet.	N	0.50374149	None	None	N
L/R	0.0973	likely_benign	0.0991	benign	-0.29	Destabilizing	1.0	D	0.745	deleterious	D	0.571020088	None	None	N
L/S	0.1784	likely_benign	0.2028	benign	-1.263	Destabilizing	0.998	D	0.741	deleterious	None	None	None	None	N
L/T	0.1228	likely_benign	0.1294	benign	-1.154	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
L/V	0.0854	likely_benign	0.0838	benign	-0.754	Destabilizing	0.992	D	0.51	neutral	D	0.525801452	None	None	N
L/W	0.2025	likely_benign	0.2039	benign	-0.908	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
L/Y	0.271	likely_benign	0.2715	benign	-0.671	Destabilizing	1.0	D	0.739	prob.delet.	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.