TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9242	27949;27950;27951	chr2:178712106;178712105;178712104	chr2:179576833;179576832;179576831
N2AB	8925	26998;26999;27000	chr2:178712106;178712105;178712104	chr2:179576833;179576832;179576831
N2A	7998	24217;24218;24219	chr2:178712106;178712105;178712104	chr2:179576833;179576832;179576831
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-78
• Domain position: 38
• Structural Position: 52
• Q(SASA): 0.8214
• 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	rs746470885	0.133	1.0	N	0.552	0.388	0.530409124356	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.66E-05	0
D/Y	rs746470885	0.133	1.0	N	0.552	0.388	0.530409124356	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
D/Y	rs746470885	0.133	1.0	N	0.552	0.388	0.530409124356	gnomAD-4.0.0	5.08171E-05	None	None	None	None	N	None	1.33518E-05	0	None	0	0	None	0	0	6.78087E-05	0	1.60138E-05

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	0.249	likely_benign	0.3048	benign	0.022	Stabilizing	0.989	D	0.421	neutral	N	0.462720006	None	None	N
D/C	0.7761	likely_pathogenic	0.8049	pathogenic	-0.123	Destabilizing	1.0	D	0.583	neutral	None	None	None	None	N
D/E	0.2257	likely_benign	0.2298	benign	-0.28	Destabilizing	0.989	D	0.457	neutral	N	0.491763842	None	None	N
D/F	0.6357	likely_pathogenic	0.6949	pathogenic	-0.027	Destabilizing	1.0	D	0.553	neutral	None	None	None	None	N
D/G	0.2124	likely_benign	0.2434	benign	-0.093	Destabilizing	0.217	N	0.307	neutral	N	0.440961302	None	None	N
D/H	0.3728	ambiguous	0.4357	ambiguous	0.579	Stabilizing	1.0	D	0.46	neutral	N	0.462239481	None	None	N
D/I	0.4671	ambiguous	0.5345	ambiguous	0.257	Stabilizing	1.0	D	0.575	neutral	None	None	None	None	N
D/K	0.4472	ambiguous	0.4938	ambiguous	0.484	Stabilizing	0.998	D	0.467	neutral	None	None	None	None	N
D/L	0.5032	ambiguous	0.5698	pathogenic	0.257	Stabilizing	0.999	D	0.565	neutral	None	None	None	None	N
D/M	0.6856	likely_pathogenic	0.7208	pathogenic	0.063	Stabilizing	1.0	D	0.574	neutral	None	None	None	None	N
D/N	0.1002	likely_benign	0.1088	benign	0.182	Stabilizing	0.733	D	0.328	neutral	N	0.453168169	None	None	N
D/P	0.735	likely_pathogenic	0.7935	pathogenic	0.198	Stabilizing	1.0	D	0.465	neutral	None	None	None	None	N
D/Q	0.4477	ambiguous	0.481	ambiguous	0.198	Stabilizing	0.999	D	0.449	neutral	None	None	None	None	N
D/R	0.5027	ambiguous	0.5665	pathogenic	0.709	Stabilizing	0.999	D	0.471	neutral	None	None	None	None	N
D/S	0.1696	likely_benign	0.1945	benign	0.104	Stabilizing	0.992	D	0.419	neutral	None	None	None	None	N
D/T	0.3407	ambiguous	0.3794	ambiguous	0.206	Stabilizing	0.998	D	0.456	neutral	None	None	None	None	N
D/V	0.3073	likely_benign	0.365	ambiguous	0.198	Stabilizing	0.999	D	0.565	neutral	N	0.478875705	None	None	N
D/W	0.9266	likely_pathogenic	0.9427	pathogenic	0.023	Stabilizing	1.0	D	0.571	neutral	None	None	None	None	N
D/Y	0.2689	likely_benign	0.3243	benign	0.201	Stabilizing	1.0	D	0.552	neutral	N	0.475988869	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.