TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18656	56191;56192;56193	chr2:178600938;178600937;178600936	chr2:179465665;179465664;179465663
N2AB	17015	51268;51269;51270	chr2:178600938;178600937;178600936	chr2:179465665;179465664;179465663
N2A	16088	48487;48488;48489	chr2:178600938;178600937;178600936	chr2:179465665;179465664;179465663
N2B	9591	28996;28997;28998	chr2:178600938;178600937;178600936	chr2:179465665;179465664;179465663
Novex-1	9716	29371;29372;29373	chr2:178600938;178600937;178600936	chr2:179465665;179465664;179465663
Novex-2	9783	29572;29573;29574	chr2:178600938;178600937;178600936	chr2:179465665;179465664;179465663
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-23
• Domain position: 78
• Structural Position: 105
• Q(SASA): 0.1816
• 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
E/G	None	None	1.0	N	0.742	0.466	0.42264334713	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
E/A	0.5046	ambiguous	0.4729	ambiguous	0.879	Stabilizing	0.999	D	0.671	neutral	N	0.471105749	None	None	N
E/C	0.9487	likely_pathogenic	0.9404	pathogenic	1.011	Stabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
E/D	0.8085	likely_pathogenic	0.778	pathogenic	-1.357	Destabilizing	0.999	D	0.548	neutral	N	0.481576682	None	None	N
E/F	0.9602	likely_pathogenic	0.9486	pathogenic	1.055	Stabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
E/G	0.771	likely_pathogenic	0.748	pathogenic	0.445	Stabilizing	1.0	D	0.742	deleterious	N	0.501580268	None	None	N
E/H	0.9046	likely_pathogenic	0.8799	pathogenic	0.841	Stabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
E/I	0.7342	likely_pathogenic	0.6801	pathogenic	2.082	Highly Stabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
E/K	0.7426	likely_pathogenic	0.725	pathogenic	0.642	Stabilizing	0.999	D	0.627	neutral	N	0.481310067	None	None	N
E/L	0.8169	likely_pathogenic	0.7863	pathogenic	2.082	Highly Stabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/M	0.7563	likely_pathogenic	0.7249	pathogenic	2.303	Highly Stabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
E/N	0.8749	likely_pathogenic	0.8458	pathogenic	-0.021	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
E/P	0.9958	likely_pathogenic	0.9956	pathogenic	1.704	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
E/Q	0.3802	ambiguous	0.3491	ambiguous	0.439	Stabilizing	1.0	D	0.667	neutral	N	0.491449703	None	None	N
E/R	0.8162	likely_pathogenic	0.7907	pathogenic	0.198	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
E/S	0.6719	likely_pathogenic	0.6296	pathogenic	-0.336	Destabilizing	0.999	D	0.649	neutral	None	None	None	None	N
E/T	0.7177	likely_pathogenic	0.6461	pathogenic	0.1	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
E/V	0.5993	likely_pathogenic	0.5392	ambiguous	1.704	Stabilizing	1.0	D	0.738	prob.delet.	N	0.508958028	None	None	N
E/W	0.9907	likely_pathogenic	0.9878	pathogenic	0.609	Stabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
E/Y	0.9407	likely_pathogenic	0.9295	pathogenic	1.23	Stabilizing	1.0	D	0.767	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.