TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2684	8275;8276;8277	chr2:178771277;178771276;178771275	chr2:179636004;179636003;179636002
N2AB	2684	8275;8276;8277	chr2:178771277;178771276;178771275	chr2:179636004;179636003;179636002
N2A	2684	8275;8276;8277	chr2:178771277;178771276;178771275	chr2:179636004;179636003;179636002
N2B	2638	8137;8138;8139	chr2:178771277;178771276;178771275	chr2:179636004;179636003;179636002
Novex-1	2638	8137;8138;8139	chr2:178771277;178771276;178771275	chr2:179636004;179636003;179636002
Novex-2	2638	8137;8138;8139	chr2:178771277;178771276;178771275	chr2:179636004;179636003;179636002
Novex-3	2684	8275;8276;8277	chr2:178771277;178771276;178771275	chr2:179636004;179636003;179636002

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-16
• Domain position: 64
• Structural Position: 148
• Q(SASA): 0.7585
• 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/G	rs1008197005	None	0.801	N	0.409	0.297	0.0884992946249	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	1.20604E-04	0	0	0	0	None	0	0	0	0	0
D/G	rs1008197005	None	0.801	N	0.409	0.297	0.0884992946249	gnomAD-4.0.0	1.02447E-05	None	None	None	None	N	None	1.18339E-04	1.69492E-05	None	0	0	None	0	0	0	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	0.1532	likely_benign	0.1552	benign	-0.149	Destabilizing	0.051	N	0.234	neutral	N	0.341972741	None	None	N
D/C	0.6852	likely_pathogenic	0.6836	pathogenic	-0.085	Destabilizing	0.998	D	0.427	neutral	None	None	None	None	N
D/E	0.1375	likely_benign	0.1446	benign	-0.249	Destabilizing	0.012	N	0.163	neutral	N	0.33315467	None	None	N
D/F	0.6648	likely_pathogenic	0.6546	pathogenic	-0.09	Destabilizing	0.991	D	0.409	neutral	None	None	None	None	N
D/G	0.1443	likely_benign	0.1437	benign	-0.311	Destabilizing	0.801	D	0.409	neutral	N	0.342227802	None	None	N
D/H	0.2988	likely_benign	0.2805	benign	0.34	Stabilizing	0.966	D	0.377	neutral	N	0.352309876	None	None	N
D/I	0.3859	ambiguous	0.4033	ambiguous	0.222	Stabilizing	0.974	D	0.433	neutral	None	None	None	None	N
D/K	0.3354	likely_benign	0.3177	benign	0.398	Stabilizing	0.728	D	0.403	neutral	None	None	None	None	N
D/L	0.4119	ambiguous	0.4124	ambiguous	0.222	Stabilizing	0.842	D	0.411	neutral	None	None	None	None	N
D/M	0.6236	likely_pathogenic	0.6339	pathogenic	0.159	Stabilizing	0.998	D	0.396	neutral	None	None	None	None	N
D/N	0.1029	likely_benign	0.1035	benign	0.063	Stabilizing	0.801	D	0.405	neutral	N	0.337106617	None	None	N
D/P	0.637	likely_pathogenic	0.6233	pathogenic	0.119	Stabilizing	0.974	D	0.379	neutral	None	None	None	None	N
D/Q	0.3087	likely_benign	0.3072	benign	0.095	Stabilizing	0.172	N	0.141	neutral	None	None	None	None	N
D/R	0.3878	ambiguous	0.3588	ambiguous	0.635	Stabilizing	0.949	D	0.395	neutral	None	None	None	None	N
D/S	0.1142	likely_benign	0.117	benign	-0.031	Destabilizing	0.525	D	0.328	neutral	None	None	None	None	N
D/T	0.2113	likely_benign	0.2163	benign	0.103	Stabilizing	0.842	D	0.379	neutral	None	None	None	None	N
D/V	0.2403	likely_benign	0.2478	benign	0.119	Stabilizing	0.801	D	0.405	neutral	N	0.426499834	None	None	N
D/W	0.8788	likely_pathogenic	0.8685	pathogenic	0.022	Stabilizing	0.998	D	0.536	neutral	None	None	None	None	N
D/Y	0.3181	likely_benign	0.2947	benign	0.149	Stabilizing	0.989	D	0.41	neutral	N	0.368036628	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.