TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14633	44122;44123;44124	chr2:178631151;178631150;178631149	chr2:179495878;179495877;179495876
N2AB	12992	39199;39200;39201	chr2:178631151;178631150;178631149	chr2:179495878;179495877;179495876
N2A	12065	36418;36419;36420	chr2:178631151;178631150;178631149	chr2:179495878;179495877;179495876
N2B	5568	16927;16928;16929	chr2:178631151;178631150;178631149	chr2:179495878;179495877;179495876
Novex-1	5693	17302;17303;17304	chr2:178631151;178631150;178631149	chr2:179495878;179495877;179495876
Novex-2	5760	17503;17504;17505	chr2:178631151;178631150;178631149	chr2:179495878;179495877;179495876
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-97
• Domain position: 48
• Structural Position: 123
• Q(SASA): 0.2778
• 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
I/F	None	None	0.144	N	0.261	0.255	0.636434440543	gnomAD-4.0.0	6.84391E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99593E-07	0	0
I/V	rs2059751227	None	0.677	N	0.349	0.128	0.511848488485	gnomAD-4.0.0	1.36878E-06	None	None	None	None	N	None	5.97836E-05	0	None	0	0	None	0	0	0	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
I/A	0.713	likely_pathogenic	0.6947	pathogenic	-2.016	Highly Destabilizing	0.969	D	0.483	neutral	None	None	None	None	N
I/C	0.8796	likely_pathogenic	0.8767	pathogenic	-1.171	Destabilizing	1.0	D	0.487	neutral	None	None	None	None	N
I/D	0.9372	likely_pathogenic	0.9414	pathogenic	-2.006	Highly Destabilizing	0.999	D	0.564	neutral	None	None	None	None	N
I/E	0.7966	likely_pathogenic	0.7959	pathogenic	-1.869	Destabilizing	0.999	D	0.566	neutral	None	None	None	None	N
I/F	0.2222	likely_benign	0.2117	benign	-1.221	Destabilizing	0.144	N	0.261	neutral	N	0.509996316	None	None	N
I/G	0.9057	likely_pathogenic	0.9084	pathogenic	-2.455	Highly Destabilizing	0.995	D	0.559	neutral	None	None	None	None	N
I/H	0.8272	likely_pathogenic	0.8309	pathogenic	-1.691	Destabilizing	1.0	D	0.567	neutral	None	None	None	None	N
I/K	0.6745	likely_pathogenic	0.7038	pathogenic	-1.576	Destabilizing	0.995	D	0.568	neutral	None	None	None	None	N
I/L	0.1772	likely_benign	0.1621	benign	-0.803	Destabilizing	0.03	N	0.115	neutral	N	0.509755779	None	None	N
I/M	0.1428	likely_benign	0.132	benign	-0.615	Destabilizing	0.677	D	0.343	neutral	N	0.513396346	None	None	N
I/N	0.6599	likely_pathogenic	0.6784	pathogenic	-1.695	Destabilizing	0.998	D	0.571	neutral	D	0.761102981	None	None	N
I/P	0.8959	likely_pathogenic	0.9098	pathogenic	-1.183	Destabilizing	0.999	D	0.568	neutral	None	None	None	None	N
I/Q	0.7032	likely_pathogenic	0.7113	pathogenic	-1.697	Destabilizing	0.995	D	0.565	neutral	None	None	None	None	N
I/R	0.5753	likely_pathogenic	0.6068	pathogenic	-1.128	Destabilizing	0.995	D	0.569	neutral	None	None	None	None	N
I/S	0.6582	likely_pathogenic	0.661	pathogenic	-2.308	Highly Destabilizing	0.994	D	0.522	neutral	D	0.60357042	None	None	N
I/T	0.545	ambiguous	0.5217	ambiguous	-2.039	Highly Destabilizing	0.979	D	0.481	neutral	D	0.59869868	None	None	N
I/V	0.1375	likely_benign	0.1226	benign	-1.183	Destabilizing	0.677	D	0.349	neutral	N	0.504548586	None	None	N
I/W	0.8211	likely_pathogenic	0.8295	pathogenic	-1.486	Destabilizing	1.0	D	0.583	neutral	None	None	None	None	N
I/Y	0.7008	likely_pathogenic	0.7096	pathogenic	-1.191	Destabilizing	0.982	D	0.507	neutral	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.