TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9130	27613;27614;27615	chr2:178712534;178712533;178712532	chr2:179577261;179577260;179577259
N2AB	8813	26662;26663;26664	chr2:178712534;178712533;178712532	chr2:179577261;179577260;179577259
N2A	7886	23881;23882;23883	chr2:178712534;178712533;178712532	chr2:179577261;179577260;179577259
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: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-77
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.4984
• 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/N	rs1316381392	-0.742	0.784	N	0.547	0.157	0.584427	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
I/N	rs1316381392	-0.742	0.784	N	0.547	0.157	0.584427	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	7.35E-05	0	0
I/N	rs1316381392	-0.742	0.784	N	0.547	0.157	0.584427	gnomAD-4.0.0	2.72701E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.64489E-05	0	1.60174E-05

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	0.4842	ambiguous	0.4894	ambiguous	-1.787	Destabilizing	0.329	N	0.417	neutral	None	None	None	None	N
I/C	0.7061	likely_pathogenic	0.7008	pathogenic	-1.099	Destabilizing	0.995	D	0.501	neutral	None	None	None	None	N
I/D	0.8435	likely_pathogenic	0.8378	pathogenic	-1.44	Destabilizing	0.828	D	0.547	neutral	None	None	None	None	N
I/E	0.7052	likely_pathogenic	0.7116	pathogenic	-1.348	Destabilizing	0.704	D	0.514	neutral	None	None	None	None	N
I/F	0.1485	likely_benign	0.1395	benign	-1.017	Destabilizing	0.927	D	0.463	neutral	N	0.45790738	None	None	N
I/G	0.7829	likely_pathogenic	0.7684	pathogenic	-2.18	Highly Destabilizing	0.828	D	0.523	neutral	None	None	None	None	N
I/H	0.4657	ambiguous	0.4651	ambiguous	-1.301	Destabilizing	0.981	D	0.516	neutral	None	None	None	None	N
I/K	0.4054	ambiguous	0.4246	ambiguous	-1.379	Destabilizing	0.031	N	0.421	neutral	None	None	None	None	N
I/L	0.1041	likely_benign	0.0933	benign	-0.736	Destabilizing	0.139	N	0.285	neutral	N	0.48039207	None	None	N
I/M	0.1236	likely_benign	0.1186	benign	-0.663	Destabilizing	0.927	D	0.479	neutral	N	0.453806	None	None	N
I/N	0.383	ambiguous	0.3843	ambiguous	-1.369	Destabilizing	0.784	D	0.547	neutral	N	0.45518515	None	None	N
I/P	0.9257	likely_pathogenic	0.902	pathogenic	-1.059	Destabilizing	0.981	D	0.568	neutral	None	None	None	None	N
I/Q	0.4686	ambiguous	0.4785	ambiguous	-1.419	Destabilizing	0.893	D	0.566	neutral	None	None	None	None	N
I/R	0.2937	likely_benign	0.3067	benign	-0.87	Destabilizing	0.007	N	0.449	neutral	None	None	None	None	N
I/S	0.3988	ambiguous	0.41	ambiguous	-1.994	Destabilizing	0.27	N	0.497	neutral	N	0.4784879	None	None	N
I/T	0.2927	likely_benign	0.3095	benign	-1.774	Destabilizing	0.01	N	0.312	neutral	N	0.41628185	None	None	N
I/V	0.0865	likely_benign	0.0914	benign	-1.059	Destabilizing	0.002	N	0.199	neutral	N	0.4366972	None	None	N
I/W	0.7481	likely_pathogenic	0.7095	pathogenic	-1.171	Destabilizing	0.995	D	0.535	neutral	None	None	None	None	N
I/Y	0.4381	ambiguous	0.4351	ambiguous	-0.935	Destabilizing	0.981	D	0.53	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.