TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17734	53425;53426;53427	chr2:178607488;178607487;178607486	chr2:179472215;179472214;179472213
N2AB	16093	48502;48503;48504	chr2:178607488;178607487;178607486	chr2:179472215;179472214;179472213
N2A	15166	45721;45722;45723	chr2:178607488;178607487;178607486	chr2:179472215;179472214;179472213
N2B	8669	26230;26231;26232	chr2:178607488;178607487;178607486	chr2:179472215;179472214;179472213
Novex-1	8794	26605;26606;26607	chr2:178607488;178607487;178607486	chr2:179472215;179472214;179472213
Novex-2	8861	26806;26807;26808	chr2:178607488;178607487;178607486	chr2:179472215;179472214;179472213
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-113
• Domain position: 58
• Structural Position: 144
• Q(SASA): 0.0862
• 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
A/T	None	None	0.576	N	0.381	0.263	0.40032279838	gnomAD-4.0.0	1.59228E-06	None	None	None	None	N	None	0	2.28666E-05	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
A/C	0.4467	ambiguous	0.4383	ambiguous	-1.7	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
A/D	0.9823	likely_pathogenic	0.9903	pathogenic	-2.338	Highly Destabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	N
A/E	0.9781	likely_pathogenic	0.9887	pathogenic	-2.289	Highly Destabilizing	0.997	D	0.702	prob.neutral	N	0.521694846	None	None	N
A/F	0.943	likely_pathogenic	0.9697	pathogenic	-1.227	Destabilizing	0.998	D	0.711	prob.delet.	None	None	None	None	N
A/G	0.475	ambiguous	0.5685	pathogenic	-1.558	Destabilizing	0.989	D	0.587	neutral	N	0.521441356	None	None	N
A/H	0.9831	likely_pathogenic	0.9895	pathogenic	-1.551	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
A/I	0.458	ambiguous	0.6045	pathogenic	-0.533	Destabilizing	0.967	D	0.646	neutral	None	None	None	None	N
A/K	0.9925	likely_pathogenic	0.9959	pathogenic	-1.392	Destabilizing	0.995	D	0.705	prob.neutral	None	None	None	None	N
A/L	0.6211	likely_pathogenic	0.7015	pathogenic	-0.533	Destabilizing	0.967	D	0.545	neutral	None	None	None	None	N
A/M	0.7052	likely_pathogenic	0.7861	pathogenic	-0.739	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
A/N	0.9199	likely_pathogenic	0.9524	pathogenic	-1.468	Destabilizing	0.998	D	0.706	prob.neutral	None	None	None	None	N
A/P	0.873	likely_pathogenic	0.9061	pathogenic	-0.736	Destabilizing	0.999	D	0.719	prob.delet.	N	0.492069701	None	None	N
A/Q	0.9675	likely_pathogenic	0.98	pathogenic	-1.589	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	N
A/R	0.9798	likely_pathogenic	0.9879	pathogenic	-1.111	Destabilizing	0.998	D	0.703	prob.neutral	None	None	None	None	N
A/S	0.1902	likely_benign	0.2044	benign	-1.837	Destabilizing	0.956	D	0.553	neutral	N	0.510590903	None	None	N
A/T	0.1596	likely_benign	0.1744	benign	-1.693	Destabilizing	0.576	D	0.381	neutral	N	0.483385659	None	None	N
A/V	0.2003	likely_benign	0.2562	benign	-0.736	Destabilizing	0.37	N	0.332	neutral	N	0.471237507	None	None	N
A/W	0.9958	likely_pathogenic	0.9977	pathogenic	-1.62	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
A/Y	0.9802	likely_pathogenic	0.9906	pathogenic	-1.197	Destabilizing	0.999	D	0.716	prob.delet.	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.