TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22626	68101;68102;68103	chr2:178579154;178579153;178579152	chr2:179443881;179443880;179443879
N2AB	20985	63178;63179;63180	chr2:178579154;178579153;178579152	chr2:179443881;179443880;179443879
N2A	20058	60397;60398;60399	chr2:178579154;178579153;178579152	chr2:179443881;179443880;179443879
N2B	13561	40906;40907;40908	chr2:178579154;178579153;178579152	chr2:179443881;179443880;179443879
Novex-1	13686	41281;41282;41283	chr2:178579154;178579153;178579152	chr2:179443881;179443880;179443879
Novex-2	13753	41482;41483;41484	chr2:178579154;178579153;178579152	chr2:179443881;179443880;179443879
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-127
• Domain position: 67
• Structural Position: 159
• Q(SASA): 0.5832
• 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
K/E	rs763810229	0.417	0.939	N	0.622	0.329	0.314417295294	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
K/E	rs763810229	0.417	0.939	N	0.622	0.329	0.314417295294	gnomAD-4.0.0	8.21192E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.07951E-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
K/A	0.4141	ambiguous	0.396	ambiguous	-0.188	Destabilizing	0.953	D	0.672	neutral	None	None	None	None	I
K/C	0.5994	likely_pathogenic	0.5985	pathogenic	-0.223	Destabilizing	0.999	D	0.773	deleterious	None	None	None	None	I
K/D	0.6821	likely_pathogenic	0.6593	pathogenic	0.064	Stabilizing	0.993	D	0.717	prob.delet.	None	None	None	None	I
K/E	0.1739	likely_benign	0.1655	benign	0.058	Stabilizing	0.939	D	0.622	neutral	N	0.431028468	None	None	I
K/F	0.8411	likely_pathogenic	0.8173	pathogenic	-0.58	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	I
K/G	0.5533	ambiguous	0.5201	ambiguous	-0.378	Destabilizing	0.993	D	0.663	neutral	None	None	None	None	I
K/H	0.2638	likely_benign	0.2651	benign	-0.891	Destabilizing	0.998	D	0.703	prob.neutral	None	None	None	None	I
K/I	0.4479	ambiguous	0.4191	ambiguous	0.231	Stabilizing	0.993	D	0.755	deleterious	None	None	None	None	I
K/L	0.462	ambiguous	0.4301	ambiguous	0.231	Stabilizing	0.986	D	0.663	neutral	None	None	None	None	I
K/M	0.276	likely_benign	0.261	benign	0.375	Stabilizing	0.999	D	0.699	prob.neutral	N	0.490153463	None	None	I
K/N	0.4621	ambiguous	0.428	ambiguous	0.259	Stabilizing	0.982	D	0.689	prob.neutral	N	0.501891275	None	None	I
K/P	0.9694	likely_pathogenic	0.966	pathogenic	0.119	Stabilizing	0.998	D	0.716	prob.delet.	None	None	None	None	I
K/Q	0.0965	likely_benign	0.0965	benign	-0.05	Destabilizing	0.982	D	0.692	prob.neutral	N	0.487095181	None	None	I
K/R	0.0727	likely_benign	0.0749	benign	0.017	Stabilizing	0.046	N	0.284	neutral	N	0.42854831	None	None	I
K/S	0.3938	ambiguous	0.3716	ambiguous	-0.314	Destabilizing	0.953	D	0.681	prob.neutral	None	None	None	None	I
K/T	0.1583	likely_benign	0.1533	benign	-0.173	Destabilizing	0.991	D	0.683	prob.neutral	N	0.445168414	None	None	I
K/V	0.3918	ambiguous	0.3704	ambiguous	0.119	Stabilizing	0.993	D	0.728	prob.delet.	None	None	None	None	I
K/W	0.7584	likely_pathogenic	0.7489	pathogenic	-0.516	Destabilizing	0.999	D	0.77	deleterious	None	None	None	None	I
K/Y	0.7011	likely_pathogenic	0.6759	pathogenic	-0.124	Destabilizing	0.998	D	0.731	prob.delet.	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.