TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17680	53263;53264;53265	chr2:178607650;178607649;178607648	chr2:179472377;179472376;179472375
N2AB	16039	48340;48341;48342	chr2:178607650;178607649;178607648	chr2:179472377;179472376;179472375
N2A	15112	45559;45560;45561	chr2:178607650;178607649;178607648	chr2:179472377;179472376;179472375
N2B	8615	26068;26069;26070	chr2:178607650;178607649;178607648	chr2:179472377;179472376;179472375
Novex-1	8740	26443;26444;26445	chr2:178607650;178607649;178607648	chr2:179472377;179472376;179472375
Novex-2	8807	26644;26645;26646	chr2:178607650;178607649;178607648	chr2:179472377;179472376;179472375
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Ig-113
• Domain position: 4
• Structural Position: 9
• Q(SASA): 0.5155
• 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/D	rs779241909	-0.131	None	N	0.214	0.158	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
G/D	rs779241909	-0.131	None	N	0.214	0.158	None	gnomAD-4.0.0	2.04601E-05	None	None	None	None	I	None	1.33586E-05	0	None	0	0	None	0	0	2.62851E-05	0	1.60241E-05
G/S	None	None	0.001	N	0.195	0.105	0.0716867268079	gnomAD-4.0.0	1.59284E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86105E-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	0.0707	likely_benign	0.0695	benign	-0.329	Destabilizing	None	N	0.147	neutral	N	0.487742968	None	None	I
G/C	0.1909	likely_benign	0.2047	benign	-1.058	Destabilizing	0.612	D	0.441	neutral	N	0.483802998	None	None	I
G/D	0.1661	likely_benign	0.193	benign	-0.578	Destabilizing	None	N	0.214	neutral	N	0.433564553	None	None	I
G/E	0.1585	likely_benign	0.19	benign	-0.724	Destabilizing	0.016	N	0.363	neutral	None	None	None	None	I
G/F	0.4968	ambiguous	0.5066	ambiguous	-1.027	Destabilizing	0.356	N	0.455	neutral	None	None	None	None	I
G/H	0.3222	likely_benign	0.3694	ambiguous	-0.373	Destabilizing	0.214	N	0.424	neutral	None	None	None	None	I
G/I	0.233	likely_benign	0.2612	benign	-0.553	Destabilizing	0.214	N	0.471	neutral	None	None	None	None	I
G/K	0.3099	likely_benign	0.3901	ambiguous	-0.751	Destabilizing	0.038	N	0.381	neutral	None	None	None	None	I
G/L	0.2939	likely_benign	0.2997	benign	-0.553	Destabilizing	0.038	N	0.387	neutral	None	None	None	None	I
G/M	0.3132	likely_benign	0.3265	benign	-0.765	Destabilizing	0.676	D	0.439	neutral	None	None	None	None	I
G/N	0.1609	likely_benign	0.1749	benign	-0.487	Destabilizing	None	N	0.162	neutral	None	None	None	None	I
G/P	0.6579	likely_pathogenic	0.6754	pathogenic	-0.454	Destabilizing	0.214	N	0.451	neutral	None	None	None	None	I
G/Q	0.2477	likely_benign	0.2801	benign	-0.722	Destabilizing	0.214	N	0.455	neutral	None	None	None	None	I
G/R	0.2606	likely_benign	0.326	benign	-0.352	Destabilizing	0.055	N	0.448	neutral	N	0.466426333	None	None	I
G/S	0.0828	likely_benign	0.0847	benign	-0.645	Destabilizing	0.001	N	0.195	neutral	N	0.472504157	None	None	I
G/T	0.0945	likely_benign	0.1027	benign	-0.723	Destabilizing	0.038	N	0.359	neutral	None	None	None	None	I
G/V	0.1426	likely_benign	0.1578	benign	-0.454	Destabilizing	0.029	N	0.427	neutral	N	0.503693855	None	None	I
G/W	0.3512	ambiguous	0.4061	ambiguous	-1.122	Destabilizing	0.864	D	0.462	neutral	None	None	None	None	I
G/Y	0.342	ambiguous	0.3781	ambiguous	-0.828	Destabilizing	0.356	N	0.457	neutral	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.