TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25149	75670;75671;75672	chr2:178570687;178570686;178570685	chr2:179435414;179435413;179435412
N2AB	23508	70747;70748;70749	chr2:178570687;178570686;178570685	chr2:179435414;179435413;179435412
N2A	22581	67966;67967;67968	chr2:178570687;178570686;178570685	chr2:179435414;179435413;179435412
N2B	16084	48475;48476;48477	chr2:178570687;178570686;178570685	chr2:179435414;179435413;179435412
Novex-1	16209	48850;48851;48852	chr2:178570687;178570686;178570685	chr2:179435414;179435413;179435412
Novex-2	16276	49051;49052;49053	chr2:178570687;178570686;178570685	chr2:179435414;179435413;179435412
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-134
• Domain position: 39
• Structural Position: 52
• Q(SASA): 0.808
• 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/V	None	None	0.317	N	0.456	0.232	0.326616659874	gnomAD-4.0.0	1.59177E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85941E-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	0.1142	likely_benign	0.1236	benign	0.086	Stabilizing	0.027	N	0.356	neutral	N	0.471772134	None	None	N
D/C	0.3522	ambiguous	0.4197	ambiguous	-0.177	Destabilizing	0.935	D	0.519	neutral	None	None	None	None	N
D/E	0.0932	likely_benign	0.1003	benign	-0.371	Destabilizing	None	N	0.194	neutral	N	0.487184742	None	None	N
D/F	0.3435	ambiguous	0.385	ambiguous	-0.075	Destabilizing	0.791	D	0.453	neutral	None	None	None	None	N
D/G	0.0947	likely_benign	0.1006	benign	0.004	Stabilizing	None	N	0.227	neutral	N	0.387089531	None	None	N
D/H	0.1551	likely_benign	0.1844	benign	0.573	Stabilizing	0.78	D	0.401	neutral	N	0.490218784	None	None	N
D/I	0.1745	likely_benign	0.1969	benign	0.233	Stabilizing	0.555	D	0.449	neutral	None	None	None	None	N
D/K	0.1669	likely_benign	0.19	benign	0.395	Stabilizing	0.081	N	0.403	neutral	None	None	None	None	N
D/L	0.203	likely_benign	0.2289	benign	0.233	Stabilizing	0.38	N	0.471	neutral	None	None	None	None	N
D/M	0.336	likely_benign	0.3729	ambiguous	-0.004	Destabilizing	0.935	D	0.459	neutral	None	None	None	None	N
D/N	0.071	likely_benign	0.074	benign	0.227	Stabilizing	0.117	N	0.443	neutral	N	0.500036609	None	None	N
D/P	0.3672	ambiguous	0.3796	ambiguous	0.201	Stabilizing	0.555	D	0.425	neutral	None	None	None	None	N
D/Q	0.1614	likely_benign	0.1854	benign	0.21	Stabilizing	0.235	N	0.409	neutral	None	None	None	None	N
D/R	0.2072	likely_benign	0.2399	benign	0.6	Stabilizing	0.235	N	0.435	neutral	None	None	None	None	N
D/S	0.0816	likely_benign	0.085	benign	0.124	Stabilizing	0.081	N	0.405	neutral	None	None	None	None	N
D/T	0.1281	likely_benign	0.1399	benign	0.196	Stabilizing	0.149	N	0.415	neutral	None	None	None	None	N
D/V	0.1237	likely_benign	0.141	benign	0.201	Stabilizing	0.317	N	0.456	neutral	N	0.502246652	None	None	N
D/W	0.6915	likely_pathogenic	0.7418	pathogenic	-0.073	Destabilizing	0.935	D	0.567	neutral	None	None	None	None	N
D/Y	0.1433	likely_benign	0.1703	benign	0.14	Stabilizing	0.741	D	0.453	neutral	N	0.490472273	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.