TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8210	24853;24854;24855	chr2:178718478;178718477;178718476	chr2:179583205;179583204;179583203
N2AB	7893	23902;23903;23904	chr2:178718478;178718477;178718476	chr2:179583205;179583204;179583203
N2A	6966	21121;21122;21123	chr2:178718478;178718477;178718476	chr2:179583205;179583204;179583203
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-67
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.7634
• Predicted PPI site: I

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/R	None	None	0.014	N	0.332	0.167	0.39619538035	gnomAD-4.0.0	1.59139E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8585E-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	0.0649	likely_benign	0.0684	benign	-0.641	Destabilizing	None	N	0.149	neutral	None	None	None	None	I
L/C	0.2228	likely_benign	0.2126	benign	-0.723	Destabilizing	0.245	N	0.305	neutral	None	None	None	None	I
L/D	0.1953	likely_benign	0.2003	benign	0.117	Stabilizing	None	N	0.186	neutral	None	None	None	None	I
L/E	0.1053	likely_benign	0.1101	benign	0.057	Stabilizing	None	N	0.186	neutral	None	None	None	None	I
L/F	0.0809	likely_benign	0.0825	benign	-0.473	Destabilizing	0.065	N	0.281	neutral	N	0.493543596	None	None	I
L/G	0.164	likely_benign	0.1759	benign	-0.829	Destabilizing	0.002	N	0.338	neutral	None	None	None	None	I
L/H	0.0831	likely_benign	0.0848	benign	-0.055	Destabilizing	0.196	N	0.406	neutral	N	0.492783128	None	None	I
L/I	0.0634	likely_benign	0.062	benign	-0.258	Destabilizing	0.014	N	0.271	neutral	N	0.501485843	None	None	I
L/K	0.0948	likely_benign	0.0991	benign	-0.371	Destabilizing	0.004	N	0.315	neutral	None	None	None	None	I
L/M	0.0801	likely_benign	0.0806	benign	-0.436	Destabilizing	0.245	N	0.314	neutral	None	None	None	None	I
L/N	0.107	likely_benign	0.1157	benign	-0.279	Destabilizing	None	N	0.205	neutral	None	None	None	None	I
L/P	0.0526	likely_benign	0.0495	benign	-0.353	Destabilizing	None	N	0.186	neutral	N	0.440781314	None	None	I
L/Q	0.0672	likely_benign	0.0703	benign	-0.424	Destabilizing	None	N	0.155	neutral	None	None	None	None	I
L/R	0.0759	likely_benign	0.0772	benign	0.105	Stabilizing	0.014	N	0.332	neutral	N	0.483375379	None	None	I
L/S	0.078	likely_benign	0.0813	benign	-0.788	Destabilizing	None	N	0.149	neutral	None	None	None	None	I
L/T	0.068	likely_benign	0.0718	benign	-0.735	Destabilizing	0.004	N	0.263	neutral	None	None	None	None	I
L/V	0.0621	likely_benign	0.0622	benign	-0.353	Destabilizing	0.003	N	0.183	neutral	N	0.520724965	None	None	I
L/W	0.136	likely_benign	0.1266	benign	-0.509	Destabilizing	0.788	D	0.318	neutral	None	None	None	None	I
L/Y	0.1397	likely_benign	0.1422	benign	-0.266	Destabilizing	0.085	N	0.369	neutral	None	None	None	None	I

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.