TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24379	73360;73361;73362	chr2:178572997;178572996;178572995	chr2:179437724;179437723;179437722
N2AB	22738	68437;68438;68439	chr2:178572997;178572996;178572995	chr2:179437724;179437723;179437722
N2A	21811	65656;65657;65658	chr2:178572997;178572996;178572995	chr2:179437724;179437723;179437722
N2B	15314	46165;46166;46167	chr2:178572997;178572996;178572995	chr2:179437724;179437723;179437722
Novex-1	15439	46540;46541;46542	chr2:178572997;178572996;178572995	chr2:179437724;179437723;179437722
Novex-2	15506	46741;46742;46743	chr2:178572997;178572996;178572995	chr2:179437724;179437723;179437722
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Fn3-65
• Domain position: 57
• Structural Position: 77
• Q(SASA): 0.067
• 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
L/R	None	None	0.989	N	0.638	0.342	0.745142704899	gnomAD-4.0.0	1.59273E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86022E-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
L/A	0.639	likely_pathogenic	0.6459	pathogenic	-2.053	Highly Destabilizing	0.842	D	0.567	neutral	None	None	None	None	N
L/C	0.6004	likely_pathogenic	0.5849	pathogenic	-1.321	Destabilizing	0.998	D	0.597	neutral	None	None	None	None	N
L/D	0.9523	likely_pathogenic	0.9486	pathogenic	-1.499	Destabilizing	0.991	D	0.669	neutral	None	None	None	None	N
L/E	0.7263	likely_pathogenic	0.7312	pathogenic	-1.278	Destabilizing	0.991	D	0.661	neutral	None	None	None	None	N
L/F	0.2703	likely_benign	0.2467	benign	-1.055	Destabilizing	0.934	D	0.653	neutral	N	0.463200532	None	None	N
L/G	0.8595	likely_pathogenic	0.8468	pathogenic	-2.597	Highly Destabilizing	0.974	D	0.657	neutral	None	None	None	None	N
L/H	0.5716	likely_pathogenic	0.5735	pathogenic	-1.903	Destabilizing	0.997	D	0.643	neutral	N	0.466163047	None	None	N
L/I	0.0914	likely_benign	0.0937	benign	-0.504	Destabilizing	0.012	N	0.44	neutral	N	0.423616053	None	None	N
L/K	0.5704	likely_pathogenic	0.5941	pathogenic	-1.287	Destabilizing	0.974	D	0.637	neutral	None	None	None	None	N
L/M	0.156	likely_benign	0.1561	benign	-0.536	Destabilizing	0.949	D	0.661	neutral	None	None	None	None	N
L/N	0.765	likely_pathogenic	0.7566	pathogenic	-1.519	Destabilizing	0.991	D	0.659	neutral	None	None	None	None	N
L/P	0.8839	likely_pathogenic	0.8615	pathogenic	-0.997	Destabilizing	0.989	D	0.663	neutral	N	0.499671249	None	None	N
L/Q	0.3872	ambiguous	0.406	ambiguous	-1.351	Destabilizing	0.991	D	0.627	neutral	None	None	None	None	N
L/R	0.5117	ambiguous	0.5382	ambiguous	-1.155	Destabilizing	0.989	D	0.638	neutral	N	0.455945604	None	None	N
L/S	0.7348	likely_pathogenic	0.7351	pathogenic	-2.347	Highly Destabilizing	0.974	D	0.642	neutral	None	None	None	None	N
L/T	0.5566	ambiguous	0.5584	ambiguous	-1.964	Destabilizing	0.842	D	0.611	neutral	None	None	None	None	N
L/V	0.1097	likely_benign	0.1153	benign	-0.997	Destabilizing	0.051	N	0.309	neutral	N	0.407761166	None	None	N
L/W	0.5124	ambiguous	0.4179	ambiguous	-1.306	Destabilizing	0.016	N	0.476	neutral	None	None	None	None	N
L/Y	0.6238	likely_pathogenic	0.5879	pathogenic	-1.003	Destabilizing	0.949	D	0.645	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.