TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28411	85456;85457;85458	chr2:178560901;178560900;178560899	chr2:179425628;179425627;179425626
N2AB	26770	80533;80534;80535	chr2:178560901;178560900;178560899	chr2:179425628;179425627;179425626
N2A	25843	77752;77753;77754	chr2:178560901;178560900;178560899	chr2:179425628;179425627;179425626
N2B	19346	58261;58262;58263	chr2:178560901;178560900;178560899	chr2:179425628;179425627;179425626
Novex-1	19471	58636;58637;58638	chr2:178560901;178560900;178560899	chr2:179425628;179425627;179425626
Novex-2	19538	58837;58838;58839	chr2:178560901;178560900;178560899	chr2:179425628;179425627;179425626
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-143
• Domain position: 54
• Structural Position: 134
• Q(SASA): 0.4029
• 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
N/D	None	None	0.014	N	0.343	0.091	0.0482279557977	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
N/S	rs1254349060	-0.503	None	N	0.105	0.092	0.0138822411134	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
N/S	rs1254349060	-0.503	None	N	0.105	0.092	0.0138822411134	gnomAD-4.0.0	6.56996E-06	None	None	None	None	N	None	2.41161E-05	0	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
N/A	0.1505	likely_benign	0.143	benign	-0.377	Destabilizing	0.004	N	0.386	neutral	None	None	None	None	N
N/C	0.1388	likely_benign	0.1352	benign	0.502	Stabilizing	None	N	0.439	neutral	None	None	None	None	N
N/D	0.103	likely_benign	0.1022	benign	-0.114	Destabilizing	0.014	N	0.343	neutral	N	0.444053693	None	None	N
N/E	0.2464	likely_benign	0.2487	benign	-0.135	Destabilizing	0.009	N	0.317	neutral	None	None	None	None	N
N/F	0.2479	likely_benign	0.2571	benign	-0.606	Destabilizing	None	N	0.372	neutral	None	None	None	None	N
N/G	0.1829	likely_benign	0.1751	benign	-0.589	Destabilizing	0.004	N	0.229	neutral	None	None	None	None	N
N/H	0.0727	likely_benign	0.0673	benign	-0.686	Destabilizing	None	N	0.166	neutral	D	0.524170702	None	None	N
N/I	0.1483	likely_benign	0.1461	benign	0.105	Stabilizing	0.017	N	0.553	neutral	N	0.497946893	None	None	N
N/K	0.1837	likely_benign	0.1816	benign	-0.052	Destabilizing	0.007	N	0.309	neutral	N	0.455636124	None	None	N
N/L	0.1657	likely_benign	0.1635	benign	0.105	Stabilizing	0.004	N	0.46	neutral	None	None	None	None	N
N/M	0.2348	likely_benign	0.2245	benign	0.577	Stabilizing	0.245	N	0.575	neutral	None	None	None	None	N
N/P	0.6855	likely_pathogenic	0.6031	pathogenic	-0.029	Destabilizing	0.044	N	0.609	neutral	None	None	None	None	N
N/Q	0.197	likely_benign	0.1887	benign	-0.402	Destabilizing	0.044	N	0.374	neutral	None	None	None	None	N
N/R	0.1786	likely_benign	0.1798	benign	-0.02	Destabilizing	0.044	N	0.363	neutral	None	None	None	None	N
N/S	0.0688	likely_benign	0.063	benign	-0.174	Destabilizing	None	N	0.105	neutral	N	0.432913979	None	None	N
N/T	0.0848	likely_benign	0.082	benign	-0.055	Destabilizing	None	N	0.122	neutral	N	0.410250551	None	None	N
N/V	0.1575	likely_benign	0.1573	benign	-0.029	Destabilizing	0.009	N	0.503	neutral	None	None	None	None	N
N/W	0.5049	ambiguous	0.512	ambiguous	-0.57	Destabilizing	0.245	N	0.579	neutral	None	None	None	None	N
N/Y	0.0742	likely_benign	0.0781	benign	-0.336	Destabilizing	None	N	0.289	neutral	N	0.494541228	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.