TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8066	24421;24422;24423	chr2:178719194;178719193;178719192	chr2:179583921;179583920;179583919
N2AB	7749	23470;23471;23472	chr2:178719194;178719193;178719192	chr2:179583921;179583920;179583919
N2A	6822	20689;20690;20691	chr2:178719194;178719193;178719192	chr2:179583921;179583920;179583919
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-65
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.214
• 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
D/N	rs755202091	-0.588	0.426	N	0.442	0.267	None	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	6.48E-05	2.9E-05	None	0	0	None	0	None	0	8.97E-06	0
D/N	rs755202091	-0.588	0.426	N	0.442	0.267	None	gnomAD-3.1.2	3.29E-05	None	None	None	None	I	None	1.20691E-04	0	0	0	0	None	0	0	0	0	0
D/N	rs755202091	-0.588	0.426	N	0.442	0.267	None	gnomAD-4.0.0	1.73544E-05	None	None	None	None	I	None	6.67628E-05	5.00117E-05	None	0	0	None	0	1.64582E-04	1.6107E-05	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	0.1732	likely_benign	0.1654	benign	-0.611	Destabilizing	None	N	0.361	neutral	N	0.431796472	None	None	I
D/C	0.7047	likely_pathogenic	0.7152	pathogenic	-0.235	Destabilizing	0.001	N	0.425	neutral	None	None	None	None	I
D/E	0.2701	likely_benign	0.2323	benign	-0.699	Destabilizing	None	N	0.089	neutral	D	0.530517884	None	None	I
D/F	0.7703	likely_pathogenic	0.7634	pathogenic	-0.21	Destabilizing	0.555	D	0.627	neutral	None	None	None	None	I
D/G	0.2348	likely_benign	0.225	benign	-0.956	Destabilizing	0.027	N	0.503	neutral	N	0.496203396	None	None	I
D/H	0.4258	ambiguous	0.4072	ambiguous	-0.481	Destabilizing	0.705	D	0.511	neutral	N	0.509534711	None	None	I
D/I	0.5509	ambiguous	0.5319	ambiguous	0.303	Stabilizing	0.38	N	0.635	neutral	None	None	None	None	I
D/K	0.4691	ambiguous	0.4403	ambiguous	-0.275	Destabilizing	0.081	N	0.517	neutral	None	None	None	None	I
D/L	0.5638	ambiguous	0.5423	ambiguous	0.303	Stabilizing	0.081	N	0.627	neutral	None	None	None	None	I
D/M	0.713	likely_pathogenic	0.725	pathogenic	0.704	Stabilizing	0.935	D	0.592	neutral	None	None	None	None	I
D/N	0.1287	likely_benign	0.1224	benign	-0.734	Destabilizing	0.426	N	0.442	neutral	N	0.490581082	None	None	I
D/P	0.9707	likely_pathogenic	0.9664	pathogenic	0.023	Stabilizing	0.555	D	0.551	neutral	None	None	None	None	I
D/Q	0.4472	ambiguous	0.4112	ambiguous	-0.619	Destabilizing	0.235	N	0.497	neutral	None	None	None	None	I
D/R	0.4915	ambiguous	0.4567	ambiguous	-0.109	Destabilizing	0.235	N	0.619	neutral	None	None	None	None	I
D/S	0.1194	likely_benign	0.1174	benign	-0.985	Destabilizing	0.007	N	0.16	neutral	None	None	None	None	I
D/T	0.319	likely_benign	0.3099	benign	-0.699	Destabilizing	0.081	N	0.495	neutral	None	None	None	None	I
D/V	0.3184	likely_benign	0.3005	benign	0.023	Stabilizing	0.062	N	0.622	neutral	N	0.468237274	None	None	I
D/W	0.9497	likely_pathogenic	0.9477	pathogenic	0.003	Stabilizing	0.935	D	0.653	neutral	None	None	None	None	I
D/Y	0.4081	ambiguous	0.3969	ambiguous	0.054	Stabilizing	0.879	D	0.628	neutral	N	0.52130909	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.