TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13744	41455;41456;41457	chr2:178636497;178636496;178636495	chr2:179501224;179501223;179501222
N2AB	12103	36532;36533;36534	chr2:178636497;178636496;178636495	chr2:179501224;179501223;179501222
N2A	11176	33751;33752;33753	chr2:178636497;178636496;178636495	chr2:179501224;179501223;179501222
N2B	4679	14260;14261;14262	chr2:178636497;178636496;178636495	chr2:179501224;179501223;179501222
Novex-1	4804	14635;14636;14637	chr2:178636497;178636496;178636495	chr2:179501224;179501223;179501222
Novex-2	4871	14836;14837;14838	chr2:178636497;178636496;178636495	chr2:179501224;179501223;179501222
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-87
• Domain position: 61
• Structural Position: 139
• Q(SASA): 0.3677
• 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
H/N	None	None	0.01	N	0.267	0.164	0.263140351381	gnomAD-4.0.0	6.84368E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99637E-07	0	0
H/R	None	None	0.642	N	0.475	0.281	0.270889551736	gnomAD-4.0.0	1.59196E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85954E-06	0	0
H/Y	rs1178244629	0.651	0.784	N	0.459	0.22	0.340273420219	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
H/Y	rs1178244629	0.651	0.784	N	0.459	0.22	0.340273420219	gnomAD-4.0.0	2.0531E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69891E-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
H/A	0.8681	likely_pathogenic	0.8738	pathogenic	-1.43	Destabilizing	0.495	N	0.473	neutral	None	None	None	None	N
H/C	0.6308	likely_pathogenic	0.6438	pathogenic	-0.652	Destabilizing	0.995	D	0.582	neutral	None	None	None	None	N
H/D	0.9407	likely_pathogenic	0.9428	pathogenic	-0.71	Destabilizing	0.27	N	0.515	neutral	N	0.497865821	None	None	N
H/E	0.8785	likely_pathogenic	0.8835	pathogenic	-0.563	Destabilizing	0.329	N	0.453	neutral	None	None	None	None	N
H/F	0.6937	likely_pathogenic	0.7295	pathogenic	0.109	Stabilizing	0.893	D	0.57	neutral	None	None	None	None	N
H/G	0.9574	likely_pathogenic	0.9616	pathogenic	-1.831	Destabilizing	0.495	N	0.471	neutral	None	None	None	None	N
H/I	0.7906	likely_pathogenic	0.8132	pathogenic	-0.286	Destabilizing	0.543	D	0.541	neutral	None	None	None	None	N
H/K	0.9098	likely_pathogenic	0.9154	pathogenic	-1.041	Destabilizing	0.329	N	0.508	neutral	None	None	None	None	N
H/L	0.3626	ambiguous	0.4067	ambiguous	-0.286	Destabilizing	0.002	N	0.531	neutral	N	0.434213769	None	None	N
H/M	0.795	likely_pathogenic	0.8254	pathogenic	-0.492	Destabilizing	0.893	D	0.547	neutral	None	None	None	None	N
H/N	0.546	ambiguous	0.5295	ambiguous	-1.252	Destabilizing	0.01	N	0.267	neutral	N	0.433405433	None	None	N
H/P	0.9852	likely_pathogenic	0.9884	pathogenic	-0.651	Destabilizing	0.975	D	0.598	neutral	N	0.5109628	None	None	N
H/Q	0.7001	likely_pathogenic	0.6964	pathogenic	-0.929	Destabilizing	0.065	N	0.273	neutral	N	0.406256312	None	None	N
H/R	0.746	likely_pathogenic	0.7512	pathogenic	-1.358	Destabilizing	0.642	D	0.475	neutral	N	0.42388416	None	None	N
H/S	0.7893	likely_pathogenic	0.7919	pathogenic	-1.481	Destabilizing	0.495	N	0.475	neutral	None	None	None	None	N
H/T	0.8779	likely_pathogenic	0.8916	pathogenic	-1.221	Destabilizing	0.704	D	0.543	neutral	None	None	None	None	N
H/V	0.7404	likely_pathogenic	0.769	pathogenic	-0.651	Destabilizing	0.543	D	0.529	neutral	None	None	None	None	N
H/W	0.7394	likely_pathogenic	0.7743	pathogenic	0.616	Stabilizing	0.995	D	0.573	neutral	None	None	None	None	N
H/Y	0.3342	likely_benign	0.3414	ambiguous	0.578	Stabilizing	0.784	D	0.459	neutral	N	0.484623344	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.