TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28538	85837;85838;85839	chr2:178560520;178560519;178560518	chr2:179425247;179425246;179425245
N2AB	26897	80914;80915;80916	chr2:178560520;178560519;178560518	chr2:179425247;179425246;179425245
N2A	25970	78133;78134;78135	chr2:178560520;178560519;178560518	chr2:179425247;179425246;179425245
N2B	19473	58642;58643;58644	chr2:178560520;178560519;178560518	chr2:179425247;179425246;179425245
Novex-1	19598	59017;59018;59019	chr2:178560520;178560519;178560518	chr2:179425247;179425246;179425245
Novex-2	19665	59218;59219;59220	chr2:178560520;178560519;178560518	chr2:179425247;179425246;179425245
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-95
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.3402
• 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
E/K	None	None	0.856	N	0.768	0.271	0.345175991111	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
E/A	0.3148	likely_benign	0.2984	benign	-0.639	Destabilizing	0.856	D	0.784	deleterious	N	0.490990296	None	None	N
E/C	0.8917	likely_pathogenic	0.8979	pathogenic	-0.327	Destabilizing	0.998	D	0.839	deleterious	None	None	None	None	N
E/D	0.3053	likely_benign	0.3001	benign	-0.828	Destabilizing	0.018	N	0.297	neutral	N	0.474567881	None	None	N
E/F	0.8069	likely_pathogenic	0.8189	pathogenic	0.271	Stabilizing	0.998	D	0.859	deleterious	None	None	None	None	N
E/G	0.4824	ambiguous	0.4475	ambiguous	-1.029	Destabilizing	0.954	D	0.791	deleterious	N	0.500460497	None	None	N
E/H	0.6675	likely_pathogenic	0.6683	pathogenic	0.237	Stabilizing	0.998	D	0.794	deleterious	None	None	None	None	N
E/I	0.4172	ambiguous	0.4103	ambiguous	0.436	Stabilizing	0.982	D	0.835	deleterious	None	None	None	None	N
E/K	0.3365	likely_benign	0.3134	benign	-0.142	Destabilizing	0.856	D	0.768	deleterious	N	0.475772876	None	None	N
E/L	0.4214	ambiguous	0.4287	ambiguous	0.436	Stabilizing	0.982	D	0.781	deleterious	None	None	None	None	N
E/M	0.5352	ambiguous	0.5371	ambiguous	0.72	Stabilizing	0.998	D	0.866	deleterious	None	None	None	None	N
E/N	0.5157	ambiguous	0.5229	ambiguous	-0.907	Destabilizing	0.932	D	0.818	deleterious	None	None	None	None	N
E/P	0.7435	likely_pathogenic	0.7595	pathogenic	0.099	Stabilizing	0.982	D	0.794	deleterious	None	None	None	None	N
E/Q	0.1959	likely_benign	0.2031	benign	-0.727	Destabilizing	0.977	D	0.805	deleterious	N	0.467125596	None	None	N
E/R	0.5007	ambiguous	0.4746	ambiguous	0.227	Stabilizing	0.982	D	0.802	deleterious	None	None	None	None	N
E/S	0.4314	ambiguous	0.4223	ambiguous	-1.195	Destabilizing	0.887	D	0.765	deleterious	None	None	None	None	N
E/T	0.3581	ambiguous	0.3463	ambiguous	-0.846	Destabilizing	0.965	D	0.765	deleterious	None	None	None	None	N
E/V	0.2363	likely_benign	0.2243	benign	0.099	Stabilizing	0.977	D	0.793	deleterious	N	0.486016773	None	None	N
E/W	0.9415	likely_pathogenic	0.9428	pathogenic	0.642	Stabilizing	0.998	D	0.845	deleterious	None	None	None	None	N
E/Y	0.7389	likely_pathogenic	0.7497	pathogenic	0.591	Stabilizing	0.998	D	0.862	deleterious	None	None	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.