TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5795	17608;17609;17610	chr2:178731383;178731382;178731381	chr2:179596110;179596109;179596108
N2AB	5478	16657;16658;16659	chr2:178731383;178731382;178731381	chr2:179596110;179596109;179596108
N2A	4551	13876;13877;13878	chr2:178731383;178731382;178731381	chr2:179596110;179596109;179596108
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: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-41
• Domain position: 66
• Structural Position: 148
• Q(SASA): 0.6096
• 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
K/E	rs1226206785	0.228	0.334	N	0.289	0.14	0.126345400529	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
K/E	rs1226206785	0.228	0.334	N	0.289	0.14	0.126345400529	gnomAD-4.0.0	3.18243E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71654E-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
K/A	0.2511	likely_benign	0.2261	benign	-0.039	Destabilizing	0.25	N	0.332	neutral	None	None	None	None	N
K/C	0.6164	likely_pathogenic	0.5763	pathogenic	-0.098	Destabilizing	0.992	D	0.279	neutral	None	None	None	None	N
K/D	0.3952	ambiguous	0.3743	ambiguous	-0.105	Destabilizing	0.447	N	0.331	neutral	None	None	None	None	N
K/E	0.1368	likely_benign	0.1353	benign	-0.073	Destabilizing	0.334	N	0.289	neutral	N	0.384342802	None	None	N
K/F	0.6424	likely_pathogenic	0.6031	pathogenic	-0.083	Destabilizing	0.972	D	0.281	neutral	None	None	None	None	N
K/G	0.3028	likely_benign	0.2772	benign	-0.282	Destabilizing	0.25	N	0.305	neutral	None	None	None	None	N
K/H	0.2538	likely_benign	0.2479	benign	-0.543	Destabilizing	0.92	D	0.311	neutral	None	None	None	None	N
K/I	0.2642	likely_benign	0.2461	benign	0.537	Stabilizing	0.92	D	0.307	neutral	None	None	None	None	N
K/L	0.2842	likely_benign	0.2631	benign	0.537	Stabilizing	0.617	D	0.319	neutral	None	None	None	None	N
K/M	0.194	likely_benign	0.183	benign	0.227	Stabilizing	0.963	D	0.314	neutral	N	0.476834462	None	None	N
K/N	0.2671	likely_benign	0.2472	benign	0.159	Stabilizing	0.002	N	0.111	neutral	N	0.392311711	None	None	N
K/P	0.5013	ambiguous	0.4622	ambiguous	0.374	Stabilizing	0.92	D	0.326	neutral	None	None	None	None	N
K/Q	0.1139	likely_benign	0.1132	benign	0.04	Stabilizing	0.549	D	0.325	neutral	N	0.430003307	None	None	N
K/R	0.0832	likely_benign	0.0819	benign	-0.14	Destabilizing	0.004	N	0.175	neutral	N	0.425424207	None	None	N
K/S	0.2636	likely_benign	0.246	benign	-0.266	Destabilizing	0.026	N	0.117	neutral	None	None	None	None	N
K/T	0.1392	likely_benign	0.1289	benign	-0.08	Destabilizing	0.379	N	0.314	neutral	N	0.427405719	None	None	N
K/V	0.2868	likely_benign	0.2612	benign	0.374	Stabilizing	0.617	D	0.311	neutral	None	None	None	None	N
K/W	0.6447	likely_pathogenic	0.6173	pathogenic	-0.116	Destabilizing	0.992	D	0.421	neutral	None	None	None	None	N
K/Y	0.5272	ambiguous	0.505	ambiguous	0.204	Stabilizing	0.972	D	0.296	neutral	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.