TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25267	76024;76025;76026	chr2:178570333;178570332;178570331	chr2:179435060;179435059;179435058
N2AB	23626	71101;71102;71103	chr2:178570333;178570332;178570331	chr2:179435060;179435059;179435058
N2A	22699	68320;68321;68322	chr2:178570333;178570332;178570331	chr2:179435060;179435059;179435058
N2B	16202	48829;48830;48831	chr2:178570333;178570332;178570331	chr2:179435060;179435059;179435058
Novex-1	16327	49204;49205;49206	chr2:178570333;178570332;178570331	chr2:179435060;179435059;179435058
Novex-2	16394	49405;49406;49407	chr2:178570333;178570332;178570331	chr2:179435060;179435059;179435058
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-71
• Domain position: 64
• Structural Position: 94
• Q(SASA): 0.4229
• 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
T/A	rs1707717762	None	0.581	N	0.417	0.195	0.27132560031	gnomAD-4.0.0	1.5924E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85946E-06	0	0
T/S	None	None	0.738	N	0.415	0.233	0.262175524916	gnomAD-4.0.0	1.5924E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85946E-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	0.1434	likely_benign	0.146	benign	-0.57	Destabilizing	0.581	D	0.417	neutral	N	0.470384961	None	None	N
T/C	0.4876	ambiguous	0.5351	ambiguous	-0.417	Destabilizing	0.993	D	0.734	prob.delet.	None	None	None	None	N
T/D	0.6838	likely_pathogenic	0.7418	pathogenic	0.127	Stabilizing	0.976	D	0.765	deleterious	None	None	None	None	N
T/E	0.6114	likely_pathogenic	0.6658	pathogenic	0.126	Stabilizing	0.929	D	0.758	deleterious	None	None	None	None	N
T/F	0.4149	ambiguous	0.4057	ambiguous	-0.607	Destabilizing	0.764	D	0.778	deleterious	None	None	None	None	N
T/G	0.2435	likely_benign	0.2589	benign	-0.82	Destabilizing	0.929	D	0.692	prob.neutral	None	None	None	None	N
T/H	0.4276	ambiguous	0.459	ambiguous	-1.006	Destabilizing	0.993	D	0.755	deleterious	None	None	None	None	N
T/I	0.3208	likely_benign	0.3467	ambiguous	-0.002	Destabilizing	0.709	D	0.684	prob.neutral	N	0.48086912	None	None	N
T/K	0.4275	ambiguous	0.4582	ambiguous	-0.625	Destabilizing	0.929	D	0.747	deleterious	None	None	None	None	N
T/L	0.1426	likely_benign	0.1178	benign	-0.002	Destabilizing	0.006	N	0.329	neutral	None	None	None	None	N
T/M	0.1242	likely_benign	0.1047	benign	0.039	Stabilizing	0.924	D	0.767	deleterious	None	None	None	None	N
T/N	0.1828	likely_benign	0.1896	benign	-0.523	Destabilizing	0.968	D	0.638	neutral	N	0.471016844	None	None	N
T/P	0.1402	likely_benign	0.1621	benign	-0.159	Destabilizing	0.968	D	0.783	deleterious	N	0.482057208	None	None	N
T/Q	0.3447	ambiguous	0.352	ambiguous	-0.627	Destabilizing	0.976	D	0.781	deleterious	None	None	None	None	N
T/R	0.3923	ambiguous	0.4262	ambiguous	-0.414	Destabilizing	0.929	D	0.783	deleterious	None	None	None	None	N
T/S	0.1424	likely_benign	0.1487	benign	-0.805	Destabilizing	0.738	D	0.415	neutral	N	0.491294987	None	None	N
T/V	0.2144	likely_benign	0.2213	benign	-0.159	Destabilizing	0.48	N	0.419	neutral	None	None	None	None	N
T/W	0.71	likely_pathogenic	0.7201	pathogenic	-0.588	Destabilizing	0.993	D	0.755	deleterious	None	None	None	None	N
T/Y	0.4744	ambiguous	0.49	ambiguous	-0.345	Destabilizing	0.929	D	0.782	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.