TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8028	24307;24308;24309	chr2:178719308;178719307;178719306	chr2:179584035;179584034;179584033
N2AB	7711	23356;23357;23358	chr2:178719308;178719307;178719306	chr2:179584035;179584034;179584033
N2A	6784	20575;20576;20577	chr2:178719308;178719307;178719306	chr2:179584035;179584034;179584033
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Ig-65
• Domain position: 44
• Structural Position: 73
• Q(SASA): 0.7253
• 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
G/A	rs560897705	-0.12	0.41	N	0.369	0.286	0.194818534648	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	6.49E-05	0
G/A	rs560897705	-0.12	0.41	N	0.369	0.286	0.194818534648	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
G/A	rs560897705	-0.12	0.41	N	0.369	0.286	0.194818534648	gnomAD-4.0.0	6.19751E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.47644E-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
G/A	0.1232	likely_benign	0.1247	benign	-0.272	Destabilizing	0.41	N	0.369	neutral	N	0.461189524	None	None	I
G/C	0.1727	likely_benign	0.1751	benign	-0.857	Destabilizing	0.98	D	0.779	deleterious	None	None	None	None	I
G/D	0.1428	likely_benign	0.1498	benign	-0.644	Destabilizing	0.764	D	0.611	neutral	None	None	None	None	I
G/E	0.1774	likely_benign	0.1953	benign	-0.819	Destabilizing	0.709	D	0.633	neutral	N	0.51127511	None	None	I
G/F	0.3389	likely_benign	0.3633	ambiguous	-1.082	Destabilizing	0.98	D	0.769	deleterious	None	None	None	None	I
G/H	0.208	likely_benign	0.2303	benign	-0.491	Destabilizing	0.98	D	0.716	prob.delet.	None	None	None	None	I
G/I	0.1916	likely_benign	0.2079	benign	-0.496	Destabilizing	0.866	D	0.774	deleterious	None	None	None	None	I
G/K	0.2657	likely_benign	0.3053	benign	-0.745	Destabilizing	0.764	D	0.607	neutral	None	None	None	None	I
G/L	0.2267	likely_benign	0.2427	benign	-0.496	Destabilizing	0.866	D	0.72	prob.delet.	None	None	None	None	I
G/M	0.3145	likely_benign	0.347	ambiguous	-0.463	Destabilizing	0.993	D	0.772	deleterious	None	None	None	None	I
G/N	0.169	likely_benign	0.1801	benign	-0.404	Destabilizing	0.764	D	0.591	neutral	None	None	None	None	I
G/P	0.6923	likely_pathogenic	0.7435	pathogenic	-0.392	Destabilizing	0.866	D	0.708	prob.delet.	None	None	None	None	I
G/Q	0.2375	likely_benign	0.2632	benign	-0.715	Destabilizing	0.866	D	0.71	prob.delet.	None	None	None	None	I
G/R	0.1942	likely_benign	0.2163	benign	-0.285	Destabilizing	0.023	N	0.354	neutral	N	0.461696503	None	None	I
G/S	0.0739	likely_benign	0.0693	benign	-0.516	Destabilizing	0.006	N	0.3	neutral	None	None	None	None	I
G/T	0.1151	likely_benign	0.1154	benign	-0.629	Destabilizing	0.764	D	0.619	neutral	None	None	None	None	I
G/V	0.149	likely_benign	0.1564	benign	-0.392	Destabilizing	0.83	D	0.731	prob.delet.	N	0.476117455	None	None	I
G/W	0.3013	likely_benign	0.3347	benign	-1.206	Destabilizing	0.991	D	0.743	deleterious	N	0.496943961	None	None	I
G/Y	0.2605	likely_benign	0.2884	benign	-0.872	Destabilizing	0.98	D	0.773	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.