TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1922	5989;5990;5991	chr2:178776100;178776099;178776098	chr2:179640827;179640826;179640825
N2AB	1922	5989;5990;5991	chr2:178776100;178776099;178776098	chr2:179640827;179640826;179640825
N2A	1922	5989;5990;5991	chr2:178776100;178776099;178776098	chr2:179640827;179640826;179640825
N2B	1876	5851;5852;5853	chr2:178776100;178776099;178776098	chr2:179640827;179640826;179640825
Novex-1	1876	5851;5852;5853	chr2:178776100;178776099;178776098	chr2:179640827;179640826;179640825
Novex-2	1876	5851;5852;5853	chr2:178776100;178776099;178776098	chr2:179640827;179640826;179640825
Novex-3	1922	5989;5990;5991	chr2:178776100;178776099;178776098	chr2:179640827;179640826;179640825

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-9
• Domain position: 82
• Structural Position: 168
• Q(SASA): 0.4377
• Predicted PPI site: I

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/K	None	None	0.999	N	0.577	0.514	0.405422107966	gnomAD-4.0.0	6.84071E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99306E-07	0	0
E/Q	rs1349924695	-0.491	1.0	N	0.641	0.381	0.423119698836	gnomAD-2.1.1	3.98E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.81E-06	0
E/Q	rs1349924695	-0.491	1.0	N	0.641	0.381	0.423119698836	gnomAD-4.0.0	6.84071E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99306E-07	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	0.3533	ambiguous	0.4533	ambiguous	-0.613	Destabilizing	0.999	D	0.701	prob.neutral	D	0.545787396	None	None	I
E/C	0.9552	likely_pathogenic	0.9696	pathogenic	-0.475	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
E/D	0.3517	ambiguous	0.3384	benign	-0.819	Destabilizing	0.999	D	0.5	neutral	D	0.564730031	None	None	I
E/F	0.9588	likely_pathogenic	0.9717	pathogenic	-0.028	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
E/G	0.5686	likely_pathogenic	0.6783	pathogenic	-0.929	Destabilizing	1.0	D	0.763	deleterious	D	0.686157184	None	None	I
E/H	0.8295	likely_pathogenic	0.8824	pathogenic	-0.009	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	I
E/I	0.699	likely_pathogenic	0.769	pathogenic	0.234	Stabilizing	1.0	D	0.814	deleterious	None	None	None	None	I
E/K	0.6516	likely_pathogenic	0.768	pathogenic	-0.354	Destabilizing	0.999	D	0.577	neutral	N	0.516741885	None	None	I
E/L	0.8322	likely_pathogenic	0.8778	pathogenic	0.234	Stabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
E/M	0.7945	likely_pathogenic	0.8498	pathogenic	0.355	Stabilizing	1.0	D	0.778	deleterious	None	None	None	None	I
E/N	0.6681	likely_pathogenic	0.6957	pathogenic	-0.869	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
E/P	0.9849	likely_pathogenic	0.9922	pathogenic	-0.027	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
E/Q	0.3156	likely_benign	0.3782	ambiguous	-0.748	Destabilizing	1.0	D	0.641	neutral	N	0.516212575	None	None	I
E/R	0.7743	likely_pathogenic	0.858	pathogenic	0.04	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
E/S	0.3473	ambiguous	0.3926	ambiguous	-1.088	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	I
E/T	0.3621	ambiguous	0.418	ambiguous	-0.827	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
E/V	0.4932	ambiguous	0.5723	pathogenic	-0.027	Destabilizing	1.0	D	0.803	deleterious	N	0.521729827	None	None	I
E/W	0.9886	likely_pathogenic	0.993	pathogenic	0.225	Stabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
E/Y	0.9377	likely_pathogenic	0.9594	pathogenic	0.218	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	I

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.