TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19724	59395;59396;59397	chr2:178592949;178592948;178592947	chr2:179457676;179457675;179457674
N2AB	18083	54472;54473;54474	chr2:178592949;178592948;178592947	chr2:179457676;179457675;179457674
N2A	17156	51691;51692;51693	chr2:178592949;178592948;178592947	chr2:179457676;179457675;179457674
N2B	10659	32200;32201;32202	chr2:178592949;178592948;178592947	chr2:179457676;179457675;179457674
Novex-1	10784	32575;32576;32577	chr2:178592949;178592948;178592947	chr2:179457676;179457675;179457674
Novex-2	10851	32776;32777;32778	chr2:178592949;178592948;178592947	chr2:179457676;179457675;179457674
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: Fn3-31
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.3836
• 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/E	rs1373178934	None	0.005	N	0.151	0.139	0.279776271856	gnomAD-4.0.0	1.3686E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79916E-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	0.1418	likely_benign	0.1379	benign	-0.205	Destabilizing	0.801	D	0.317	neutral	N	0.430494458	None	None	N
D/C	0.4582	ambiguous	0.4522	ambiguous	0.096	Stabilizing	0.998	D	0.467	neutral	None	None	None	None	N
D/E	0.1028	likely_benign	0.1044	benign	-0.34	Destabilizing	0.005	N	0.151	neutral	N	0.416274367	None	None	N
D/F	0.4739	ambiguous	0.491	ambiguous	-0.301	Destabilizing	0.904	D	0.44	neutral	None	None	None	None	N
D/G	0.1649	likely_benign	0.1565	benign	-0.385	Destabilizing	0.012	N	0.235	neutral	N	0.430281027	None	None	N
D/H	0.2587	likely_benign	0.2409	benign	-0.225	Destabilizing	0.966	D	0.305	neutral	N	0.509493959	None	None	N
D/I	0.2876	likely_benign	0.3037	benign	0.215	Stabilizing	0.974	D	0.447	neutral	None	None	None	None	N
D/K	0.2859	likely_benign	0.2849	benign	0.259	Stabilizing	0.728	D	0.276	neutral	None	None	None	None	N
D/L	0.2734	likely_benign	0.2835	benign	0.215	Stabilizing	0.949	D	0.435	neutral	None	None	None	None	N
D/M	0.4077	ambiguous	0.4247	ambiguous	0.357	Stabilizing	0.998	D	0.426	neutral	None	None	None	None	N
D/N	0.1038	likely_benign	0.0983	benign	0.107	Stabilizing	0.801	D	0.346	neutral	N	0.460430576	None	None	N
D/P	0.7482	likely_pathogenic	0.7654	pathogenic	0.097	Stabilizing	0.974	D	0.325	neutral	None	None	None	None	N
D/Q	0.2337	likely_benign	0.2292	benign	0.112	Stabilizing	0.904	D	0.29	neutral	None	None	None	None	N
D/R	0.3326	likely_benign	0.3286	benign	0.361	Stabilizing	0.949	D	0.406	neutral	None	None	None	None	N
D/S	0.1117	likely_benign	0.1055	benign	-0.014	Destabilizing	0.842	D	0.261	neutral	None	None	None	None	N
D/T	0.172	likely_benign	0.1665	benign	0.116	Stabilizing	0.842	D	0.31	neutral	None	None	None	None	N
D/V	0.1656	likely_benign	0.1722	benign	0.097	Stabilizing	0.966	D	0.436	neutral	N	0.48523302	None	None	N
D/W	0.7632	likely_pathogenic	0.7781	pathogenic	-0.235	Destabilizing	0.998	D	0.462	neutral	None	None	None	None	N
D/Y	0.2104	likely_benign	0.2092	benign	-0.085	Destabilizing	0.111	N	0.349	neutral	N	0.473886772	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.