TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32221	96886;96887;96888	chr2:178543312;178543311;178543310	chr2:179408039;179408038;179408037
N2AB	30580	91963;91964;91965	chr2:178543312;178543311;178543310	chr2:179408039;179408038;179408037
N2A	29653	89182;89183;89184	chr2:178543312;178543311;178543310	chr2:179408039;179408038;179408037
N2B	23156	69691;69692;69693	chr2:178543312;178543311;178543310	chr2:179408039;179408038;179408037
Novex-1	23281	70066;70067;70068	chr2:178543312;178543311;178543310	chr2:179408039;179408038;179408037
Novex-2	23348	70267;70268;70269	chr2:178543312;178543311;178543310	chr2:179408039;179408038;179408037
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: Fn3-123
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.1041
• 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/V	rs1695511296	None	0.05	N	0.616	0.181	0.448597761117	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.8436	likely_pathogenic	0.8451	pathogenic	-2.652	Highly Destabilizing	0.962	D	0.71	prob.delet.	None	None	None	None	N
L/C	0.8731	likely_pathogenic	0.8777	pathogenic	-1.714	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
L/D	0.9991	likely_pathogenic	0.9993	pathogenic	-3.305	Highly Destabilizing	1.0	D	0.935	deleterious	None	None	None	None	N
L/E	0.9933	likely_pathogenic	0.9948	pathogenic	-2.962	Highly Destabilizing	1.0	D	0.92	deleterious	None	None	None	None	N
L/F	0.4902	ambiguous	0.4758	ambiguous	-1.561	Destabilizing	0.964	D	0.707	prob.neutral	D	0.52312538	None	None	N
L/G	0.982	likely_pathogenic	0.9843	pathogenic	-3.278	Highly Destabilizing	1.0	D	0.918	deleterious	None	None	None	None	N
L/H	0.9842	likely_pathogenic	0.9861	pathogenic	-3.079	Highly Destabilizing	0.998	D	0.911	deleterious	D	0.551397852	None	None	N
L/I	0.1404	likely_benign	0.1362	benign	-0.755	Destabilizing	0.004	N	0.329	neutral	N	0.51752437	None	None	N
L/K	0.9882	likely_pathogenic	0.991	pathogenic	-1.93	Destabilizing	0.994	D	0.9	deleterious	None	None	None	None	N
L/M	0.2411	likely_benign	0.2483	benign	-0.974	Destabilizing	0.914	D	0.7	prob.neutral	None	None	None	None	N
L/N	0.9949	likely_pathogenic	0.9962	pathogenic	-2.714	Highly Destabilizing	1.0	D	0.937	deleterious	None	None	None	None	N
L/P	0.9896	likely_pathogenic	0.9912	pathogenic	-1.381	Destabilizing	1.0	D	0.935	deleterious	D	0.551397852	None	None	N
L/Q	0.9765	likely_pathogenic	0.9808	pathogenic	-2.288	Highly Destabilizing	1.0	D	0.93	deleterious	None	None	None	None	N
L/R	0.9759	likely_pathogenic	0.9805	pathogenic	-2.157	Highly Destabilizing	0.999	D	0.921	deleterious	D	0.551397852	None	None	N
L/S	0.9827	likely_pathogenic	0.9838	pathogenic	-3.22	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
L/T	0.8962	likely_pathogenic	0.9071	pathogenic	-2.702	Highly Destabilizing	0.964	D	0.759	deleterious	None	None	None	None	N
L/V	0.1379	likely_benign	0.1327	benign	-1.381	Destabilizing	0.05	N	0.616	neutral	N	0.473676644	None	None	N
L/W	0.9362	likely_pathogenic	0.9424	pathogenic	-1.925	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
L/Y	0.9512	likely_pathogenic	0.9545	pathogenic	-1.74	Destabilizing	0.894	D	0.822	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.