TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25814	77665;77666;77667	chr2:178568692;178568691;178568690	chr2:179433419;179433418;179433417
N2AB	24173	72742;72743;72744	chr2:178568692;178568691;178568690	chr2:179433419;179433418;179433417
N2A	23246	69961;69962;69963	chr2:178568692;178568691;178568690	chr2:179433419;179433418;179433417
N2B	16749	50470;50471;50472	chr2:178568692;178568691;178568690	chr2:179433419;179433418;179433417
Novex-1	16874	50845;50846;50847	chr2:178568692;178568691;178568690	chr2:179433419;179433418;179433417
Novex-2	16941	51046;51047;51048	chr2:178568692;178568691;178568690	chr2:179433419;179433418;179433417
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-136
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.7495
• 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
D/Y	rs1432951481	-0.084	0.999	N	0.723	0.35	0.264547087235	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
D/Y	rs1432951481	-0.084	0.999	N	0.723	0.35	0.264547087235	gnomAD-4.0.0	5.47519E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.19686E-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
D/A	0.3829	ambiguous	0.3915	ambiguous	-0.391	Destabilizing	0.988	D	0.655	neutral	N	0.504655782	None	None	N
D/C	0.8219	likely_pathogenic	0.8306	pathogenic	0.009	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
D/E	0.3291	likely_benign	0.3325	benign	-0.48	Destabilizing	0.958	D	0.475	neutral	N	0.501095402	None	None	N
D/F	0.7987	likely_pathogenic	0.8018	pathogenic	-0.351	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
D/G	0.393	ambiguous	0.3959	ambiguous	-0.645	Destabilizing	0.919	D	0.66	neutral	N	0.483697871	None	None	N
D/H	0.5455	ambiguous	0.5658	pathogenic	-0.544	Destabilizing	0.998	D	0.697	prob.neutral	N	0.466354084	None	None	N
D/I	0.6108	likely_pathogenic	0.6269	pathogenic	0.245	Stabilizing	0.995	D	0.747	deleterious	None	None	None	None	N
D/K	0.7659	likely_pathogenic	0.7732	pathogenic	0.008	Stabilizing	0.991	D	0.675	prob.neutral	None	None	None	None	N
D/L	0.6344	likely_pathogenic	0.6391	pathogenic	0.245	Stabilizing	0.995	D	0.721	prob.delet.	None	None	None	None	N
D/M	0.8014	likely_pathogenic	0.8058	pathogenic	0.585	Stabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
D/N	0.1462	likely_benign	0.1471	benign	-0.274	Destabilizing	0.142	N	0.352	neutral	N	0.478026541	None	None	N
D/P	0.6667	likely_pathogenic	0.676	pathogenic	0.057	Stabilizing	0.998	D	0.701	prob.neutral	None	None	None	None	N
D/Q	0.6488	likely_pathogenic	0.6556	pathogenic	-0.215	Destabilizing	0.991	D	0.698	prob.neutral	None	None	None	None	N
D/R	0.8013	likely_pathogenic	0.8101	pathogenic	0.088	Stabilizing	0.991	D	0.71	prob.delet.	None	None	None	None	N
D/S	0.258	likely_benign	0.2647	benign	-0.431	Destabilizing	0.938	D	0.654	neutral	None	None	None	None	N
D/T	0.4178	ambiguous	0.4325	ambiguous	-0.234	Destabilizing	0.991	D	0.684	prob.neutral	None	None	None	None	N
D/V	0.4207	ambiguous	0.43	ambiguous	0.057	Stabilizing	0.994	D	0.72	prob.delet.	N	0.490014403	None	None	N
D/W	0.9653	likely_pathogenic	0.966	pathogenic	-0.242	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
D/Y	0.4022	ambiguous	0.4078	ambiguous	-0.131	Destabilizing	0.999	D	0.723	prob.delet.	N	0.468329094	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.