TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16781	50566;50567;50568	chr2:178612070;178612069;178612068	chr2:179476797;179476796;179476795
N2AB	15140	45643;45644;45645	chr2:178612070;178612069;178612068	chr2:179476797;179476796;179476795
N2A	14213	42862;42863;42864	chr2:178612070;178612069;178612068	chr2:179476797;179476796;179476795
N2B	7716	23371;23372;23373	chr2:178612070;178612069;178612068	chr2:179476797;179476796;179476795
Novex-1	7841	23746;23747;23748	chr2:178612070;178612069;178612068	chr2:179476797;179476796;179476795
Novex-2	7908	23947;23948;23949	chr2:178612070;178612069;178612068	chr2:179476797;179476796;179476795
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-10
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.3404
• 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
R/K	rs764363428	-0.708	0.014	N	0.379	0.097	0.240491677333	gnomAD-2.1.1	4.08E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	9.02E-06	0
R/K	rs764363428	-0.708	0.014	N	0.379	0.097	0.240491677333	gnomAD-4.0.0	1.59878E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86812E-06	0	0
R/T	None	None	0.942	N	0.632	0.324	0.33340067248	gnomAD-4.0.0	1.59878E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86812E-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
R/A	0.8103	likely_pathogenic	0.8521	pathogenic	-0.089	Destabilizing	0.754	D	0.603	neutral	None	None	None	None	I
R/C	0.3759	ambiguous	0.4423	ambiguous	-0.067	Destabilizing	0.998	D	0.781	deleterious	None	None	None	None	I
R/D	0.9706	likely_pathogenic	0.9818	pathogenic	-0.029	Destabilizing	0.956	D	0.69	prob.neutral	None	None	None	None	I
R/E	0.855	likely_pathogenic	0.897	pathogenic	0.042	Stabilizing	0.754	D	0.631	neutral	None	None	None	None	I
R/F	0.8502	likely_pathogenic	0.9028	pathogenic	-0.234	Destabilizing	0.993	D	0.737	prob.delet.	None	None	None	None	I
R/G	0.7109	likely_pathogenic	0.7658	pathogenic	-0.315	Destabilizing	0.822	D	0.654	neutral	N	0.454010384	None	None	I
R/H	0.2393	likely_benign	0.3129	benign	-0.812	Destabilizing	0.978	D	0.657	neutral	None	None	None	None	I
R/I	0.7266	likely_pathogenic	0.8162	pathogenic	0.48	Stabilizing	0.971	D	0.739	prob.delet.	N	0.474985199	None	None	I
R/K	0.1376	likely_benign	0.1304	benign	-0.1	Destabilizing	0.014	N	0.379	neutral	N	0.482754917	None	None	I
R/L	0.551	ambiguous	0.6526	pathogenic	0.48	Stabilizing	0.86	D	0.654	neutral	None	None	None	None	I
R/M	0.6447	likely_pathogenic	0.7355	pathogenic	0.127	Stabilizing	0.998	D	0.618	neutral	None	None	None	None	I
R/N	0.8982	likely_pathogenic	0.9307	pathogenic	0.283	Stabilizing	0.956	D	0.677	prob.neutral	None	None	None	None	I
R/P	0.9839	likely_pathogenic	0.9895	pathogenic	0.312	Stabilizing	0.978	D	0.709	prob.delet.	None	None	None	None	I
R/Q	0.2257	likely_benign	0.277	benign	0.127	Stabilizing	0.956	D	0.691	prob.neutral	None	None	None	None	I
R/S	0.8499	likely_pathogenic	0.9009	pathogenic	-0.158	Destabilizing	0.822	D	0.665	neutral	N	0.41550835	None	None	I
R/T	0.7819	likely_pathogenic	0.8654	pathogenic	0.057	Stabilizing	0.942	D	0.632	neutral	N	0.462085407	None	None	I
R/V	0.7765	likely_pathogenic	0.844	pathogenic	0.312	Stabilizing	0.956	D	0.729	prob.delet.	None	None	None	None	I
R/W	0.594	likely_pathogenic	0.685	pathogenic	-0.197	Destabilizing	0.998	D	0.785	deleterious	None	None	None	None	I
R/Y	0.7572	likely_pathogenic	0.8222	pathogenic	0.194	Stabilizing	0.993	D	0.711	prob.delet.	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.