TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33443	100552;100553;100554	chr2:178536420;178536419;178536418	chr2:179401147;179401146;179401145
N2AB	31802	95629;95630;95631	chr2:178536420;178536419;178536418	chr2:179401147;179401146;179401145
N2A	30875	92848;92849;92850	chr2:178536420;178536419;178536418	chr2:179401147;179401146;179401145
N2B	24378	73357;73358;73359	chr2:178536420;178536419;178536418	chr2:179401147;179401146;179401145
Novex-1	24503	73732;73733;73734	chr2:178536420;178536419;178536418	chr2:179401147;179401146;179401145
Novex-2	24570	73933;73934;73935	chr2:178536420;178536419;178536418	chr2:179401147;179401146;179401145
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-131
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.1807
• 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
T/K	None	None	0.999	N	0.692	0.429	0.476522311808	gnomAD-4.0.0	1.59213E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85936E-06	0	0
T/R	None	None	0.999	N	0.748	0.442	0.620746667299	gnomAD-4.0.0	1.59213E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85936E-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
T/A	0.264	likely_benign	0.3237	benign	-0.677	Destabilizing	0.981	D	0.469	neutral	N	0.462764379	None	None	I
T/C	0.6932	likely_pathogenic	0.7198	pathogenic	-0.472	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	I
T/D	0.7995	likely_pathogenic	0.8478	pathogenic	0.499	Stabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	I
T/E	0.8322	likely_pathogenic	0.8871	pathogenic	0.473	Stabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	I
T/F	0.7971	likely_pathogenic	0.8627	pathogenic	-1.115	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
T/G	0.5496	ambiguous	0.5777	pathogenic	-0.849	Destabilizing	0.997	D	0.598	neutral	None	None	None	None	I
T/H	0.7324	likely_pathogenic	0.7864	pathogenic	-1.117	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
T/I	0.6504	likely_pathogenic	0.7383	pathogenic	-0.33	Destabilizing	0.999	D	0.751	deleterious	N	0.506957873	None	None	I
T/K	0.7427	likely_pathogenic	0.8401	pathogenic	-0.317	Destabilizing	0.999	D	0.692	prob.neutral	N	0.521156535	None	None	I
T/L	0.4216	ambiguous	0.4916	ambiguous	-0.33	Destabilizing	0.998	D	0.575	neutral	None	None	None	None	I
T/M	0.3198	likely_benign	0.376	ambiguous	-0.257	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	I
T/N	0.298	likely_benign	0.3132	benign	-0.259	Destabilizing	0.999	D	0.694	prob.neutral	None	None	None	None	I
T/P	0.7359	likely_pathogenic	0.8181	pathogenic	-0.416	Destabilizing	0.999	D	0.753	deleterious	N	0.47566488	None	None	I
T/Q	0.704	likely_pathogenic	0.7875	pathogenic	-0.351	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
T/R	0.6867	likely_pathogenic	0.8066	pathogenic	-0.192	Destabilizing	0.999	D	0.748	deleterious	N	0.506341798	None	None	I
T/S	0.2556	likely_benign	0.2553	benign	-0.554	Destabilizing	0.905	D	0.403	neutral	N	0.469495563	None	None	I
T/V	0.4996	ambiguous	0.5757	pathogenic	-0.416	Destabilizing	0.998	D	0.556	neutral	None	None	None	None	I
T/W	0.9556	likely_pathogenic	0.9715	pathogenic	-1.093	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
T/Y	0.8377	likely_pathogenic	0.8864	pathogenic	-0.802	Destabilizing	1.0	D	0.785	deleterious	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.