TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22849	68770;68771;68772	chr2:178577881;178577880;178577879	chr2:179442608;179442607;179442606
N2AB	21208	63847;63848;63849	chr2:178577881;178577880;178577879	chr2:179442608;179442607;179442606
N2A	20281	61066;61067;61068	chr2:178577881;178577880;178577879	chr2:179442608;179442607;179442606
N2B	13784	41575;41576;41577	chr2:178577881;178577880;178577879	chr2:179442608;179442607;179442606
Novex-1	13909	41950;41951;41952	chr2:178577881;178577880;178577879	chr2:179442608;179442607;179442606
Novex-2	13976	42151;42152;42153	chr2:178577881;178577880;178577879	chr2:179442608;179442607;179442606
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-54
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.5684
• 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
E/K	None	None	0.014	N	0.203	0.156	0.232513804876	gnomAD-4.0.0	1.3967E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.10584E-07	1.23864E-05	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
E/A	0.2011	likely_benign	0.1959	benign	-0.467	Destabilizing	0.698	D	0.593	neutral	N	0.483623689	None	None	N
E/C	0.8474	likely_pathogenic	0.8535	pathogenic	-0.458	Destabilizing	0.998	D	0.814	deleterious	None	None	None	None	N
E/D	0.1587	likely_benign	0.1669	benign	-0.733	Destabilizing	0.006	N	0.127	neutral	D	0.524618127	None	None	N
E/F	0.7986	likely_pathogenic	0.7973	pathogenic	0.136	Stabilizing	0.993	D	0.77	deleterious	None	None	None	None	N
E/G	0.3321	likely_benign	0.3317	benign	-0.778	Destabilizing	0.822	D	0.635	neutral	N	0.505615512	None	None	N
E/H	0.4617	ambiguous	0.4696	ambiguous	0.213	Stabilizing	0.978	D	0.589	neutral	None	None	None	None	N
E/I	0.3307	likely_benign	0.3225	benign	0.362	Stabilizing	0.978	D	0.773	deleterious	None	None	None	None	N
E/K	0.1619	likely_benign	0.1541	benign	-0.262	Destabilizing	0.014	N	0.203	neutral	N	0.494985867	None	None	N
E/L	0.4476	ambiguous	0.4344	ambiguous	0.362	Stabilizing	0.956	D	0.689	prob.neutral	None	None	None	None	N
E/M	0.4554	ambiguous	0.4501	ambiguous	0.378	Stabilizing	0.998	D	0.733	prob.delet.	None	None	None	None	N
E/N	0.2691	likely_benign	0.2781	benign	-0.792	Destabilizing	0.86	D	0.531	neutral	None	None	None	None	N
E/P	0.9548	likely_pathogenic	0.9492	pathogenic	0.107	Stabilizing	0.978	D	0.665	neutral	None	None	None	None	N
E/Q	0.1419	likely_benign	0.1395	benign	-0.661	Destabilizing	0.822	D	0.557	neutral	N	0.519460237	None	None	N
E/R	0.2658	likely_benign	0.2612	benign	0.143	Stabilizing	0.754	D	0.541	neutral	None	None	None	None	N
E/S	0.2407	likely_benign	0.246	benign	-1.001	Destabilizing	0.86	D	0.533	neutral	None	None	None	None	N
E/T	0.2234	likely_benign	0.2269	benign	-0.742	Destabilizing	0.86	D	0.625	neutral	None	None	None	None	N
E/V	0.1931	likely_benign	0.1861	benign	0.107	Stabilizing	0.942	D	0.672	neutral	D	0.523193975	None	None	N
E/W	0.9248	likely_pathogenic	0.9254	pathogenic	0.369	Stabilizing	0.998	D	0.795	deleterious	None	None	None	None	N
E/Y	0.6926	likely_pathogenic	0.6901	pathogenic	0.379	Stabilizing	0.993	D	0.757	deleterious	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.