TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33008	99247;99248;99249	chr2:178538807;178538806;178538805	chr2:179403534;179403533;179403532
N2AB	31367	94324;94325;94326	chr2:178538807;178538806;178538805	chr2:179403534;179403533;179403532
N2A	30440	91543;91544;91545	chr2:178538807;178538806;178538805	chr2:179403534;179403533;179403532
N2B	23943	72052;72053;72054	chr2:178538807;178538806;178538805	chr2:179403534;179403533;179403532
Novex-1	24068	72427;72428;72429	chr2:178538807;178538806;178538805	chr2:179403534;179403533;179403532
Novex-2	24135	72628;72629;72630	chr2:178538807;178538806;178538805	chr2:179403534;179403533;179403532
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: Fn3-129
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.3901
• 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/F	rs771594208	None	0.966	N	0.427	0.191	0.552698843619	gnomAD-4.0.0	2.74186E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.60292E-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	0.1214	likely_benign	0.1379	benign	-0.999	Destabilizing	0.525	D	0.404	neutral	None	None	None	None	N
L/C	0.3087	likely_benign	0.3551	ambiguous	-0.813	Destabilizing	0.998	D	0.429	neutral	None	None	None	None	N
L/D	0.4561	ambiguous	0.5202	ambiguous	-0.394	Destabilizing	0.949	D	0.475	neutral	None	None	None	None	N
L/E	0.2434	likely_benign	0.2647	benign	-0.448	Destabilizing	0.842	D	0.478	neutral	None	None	None	None	N
L/F	0.107	likely_benign	0.133	benign	-0.709	Destabilizing	0.966	D	0.427	neutral	N	0.511131542	None	None	N
L/G	0.3161	likely_benign	0.3714	ambiguous	-1.232	Destabilizing	0.842	D	0.467	neutral	None	None	None	None	N
L/H	0.1309	likely_benign	0.1527	benign	-0.338	Destabilizing	0.997	D	0.439	neutral	N	0.457721132	None	None	N
L/I	0.0605	likely_benign	0.0591	benign	-0.479	Destabilizing	0.022	N	0.091	neutral	N	0.441058168	None	None	N
L/K	0.1834	likely_benign	0.2008	benign	-0.663	Destabilizing	0.842	D	0.447	neutral	None	None	None	None	N
L/M	0.0905	likely_benign	0.0881	benign	-0.489	Destabilizing	0.974	D	0.467	neutral	None	None	None	None	N
L/N	0.1864	likely_benign	0.2162	benign	-0.504	Destabilizing	0.949	D	0.482	neutral	None	None	None	None	N
L/P	0.5243	ambiguous	0.6369	pathogenic	-0.619	Destabilizing	0.966	D	0.479	neutral	N	0.518500231	None	None	N
L/Q	0.1039	likely_benign	0.1112	benign	-0.717	Destabilizing	0.974	D	0.461	neutral	None	None	None	None	N
L/R	0.1463	likely_benign	0.171	benign	-0.04	Destabilizing	0.934	D	0.473	neutral	N	0.458297135	None	None	N
L/S	0.1215	likely_benign	0.1442	benign	-1.047	Destabilizing	0.728	D	0.424	neutral	None	None	None	None	N
L/T	0.0862	likely_benign	0.0867	benign	-0.988	Destabilizing	0.029	N	0.157	neutral	None	None	None	None	N
L/V	0.0659	likely_benign	0.0627	benign	-0.619	Destabilizing	0.022	N	0.107	neutral	N	0.408639105	None	None	N
L/W	0.2461	likely_benign	0.3026	benign	-0.708	Destabilizing	0.998	D	0.46	neutral	None	None	None	None	N
L/Y	0.255	likely_benign	0.3148	benign	-0.49	Destabilizing	0.991	D	0.467	neutral	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.