TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31005	93238;93239;93240	chr2:178548613;178548612;178548611	chr2:179413340;179413339;179413338
N2AB	29364	88315;88316;88317	chr2:178548613;178548612;178548611	chr2:179413340;179413339;179413338
N2A	28437	85534;85535;85536	chr2:178548613;178548612;178548611	chr2:179413340;179413339;179413338
N2B	21940	66043;66044;66045	chr2:178548613;178548612;178548611	chr2:179413340;179413339;179413338
Novex-1	22065	66418;66419;66420	chr2:178548613;178548612;178548611	chr2:179413340;179413339;179413338
Novex-2	22132	66619;66620;66621	chr2:178548613;178548612;178548611	chr2:179413340;179413339;179413338
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-150
• Domain position: 79
• Structural Position: 166
• Q(SASA): 0.5163
• 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/Q	None	None	0.957	D	0.314	0.303	0.33835085245	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
K/A	0.5957	likely_pathogenic	0.6329	pathogenic	0.056	Stabilizing	0.997	D	0.58	neutral	None	None	None	None	I
K/C	0.8086	likely_pathogenic	0.8111	pathogenic	-0.295	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	I
K/D	0.9028	likely_pathogenic	0.9108	pathogenic	0.057	Stabilizing	0.999	D	0.665	neutral	None	None	None	None	I
K/E	0.51	ambiguous	0.5675	pathogenic	0.043	Stabilizing	0.992	D	0.494	neutral	D	0.526938861	None	None	I
K/F	0.9487	likely_pathogenic	0.952	pathogenic	-0.307	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
K/G	0.7858	likely_pathogenic	0.7931	pathogenic	-0.08	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	I
K/H	0.5246	ambiguous	0.5376	ambiguous	-0.31	Destabilizing	1.0	D	0.636	neutral	None	None	None	None	I
K/I	0.7078	likely_pathogenic	0.722	pathogenic	0.325	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
K/L	0.7072	likely_pathogenic	0.7108	pathogenic	0.325	Stabilizing	1.0	D	0.657	neutral	None	None	None	None	I
K/M	0.5529	ambiguous	0.5689	pathogenic	0.121	Stabilizing	1.0	D	0.635	neutral	N	0.511015968	None	None	I
K/N	0.7918	likely_pathogenic	0.8094	pathogenic	0.207	Stabilizing	0.999	D	0.639	neutral	N	0.503000571	None	None	I
K/P	0.9849	likely_pathogenic	0.9824	pathogenic	0.26	Stabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	I
K/Q	0.2487	likely_benign	0.2681	benign	0.045	Stabilizing	0.957	D	0.314	neutral	D	0.523687912	None	None	I
K/R	0.1079	likely_benign	0.1084	benign	0.01	Stabilizing	0.996	D	0.507	neutral	D	0.530133882	None	None	I
K/S	0.6938	likely_pathogenic	0.7235	pathogenic	-0.233	Destabilizing	0.997	D	0.577	neutral	None	None	None	None	I
K/T	0.4247	ambiguous	0.4578	ambiguous	-0.119	Destabilizing	0.999	D	0.665	neutral	D	0.527979011	None	None	I
K/V	0.5955	likely_pathogenic	0.6105	pathogenic	0.26	Stabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	I
K/W	0.9559	likely_pathogenic	0.9562	pathogenic	-0.374	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	I
K/Y	0.8895	likely_pathogenic	0.8937	pathogenic	0.002	Stabilizing	1.0	D	0.687	prob.neutral	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.