TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24902	74929;74930;74931	chr2:178571428;178571427;178571426	chr2:179436155;179436154;179436153
N2AB	23261	70006;70007;70008	chr2:178571428;178571427;178571426	chr2:179436155;179436154;179436153
N2A	22334	67225;67226;67227	chr2:178571428;178571427;178571426	chr2:179436155;179436154;179436153
N2B	15837	47734;47735;47736	chr2:178571428;178571427;178571426	chr2:179436155;179436154;179436153
Novex-1	15962	48109;48110;48111	chr2:178571428;178571427;178571426	chr2:179436155;179436154;179436153
Novex-2	16029	48310;48311;48312	chr2:178571428;178571427;178571426	chr2:179436155;179436154;179436153
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-68
• Domain position: 95
• Structural Position: 130
• Q(SASA): 0.1312
• 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/V	None	None	0.125	N	0.402	0.206	0.359763055319	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
A/C	0.6135	likely_pathogenic	0.6179	pathogenic	-1.801	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
A/D	0.9984	likely_pathogenic	0.998	pathogenic	-2.763	Highly Destabilizing	0.998	D	0.877	deleterious	N	0.516184895	None	None	N
A/E	0.995	likely_pathogenic	0.9932	pathogenic	-2.679	Highly Destabilizing	0.995	D	0.833	deleterious	None	None	None	None	N
A/F	0.9503	likely_pathogenic	0.9393	pathogenic	-1.053	Destabilizing	0.995	D	0.87	deleterious	None	None	None	None	N
A/G	0.7425	likely_pathogenic	0.705	pathogenic	-1.481	Destabilizing	0.976	D	0.685	prob.delet.	N	0.515424427	None	None	N
A/H	0.9968	likely_pathogenic	0.9956	pathogenic	-1.56	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
A/I	0.4256	ambiguous	0.4449	ambiguous	-0.339	Destabilizing	0.929	D	0.759	deleterious	None	None	None	None	N
A/K	0.9981	likely_pathogenic	0.9972	pathogenic	-1.364	Destabilizing	0.995	D	0.833	deleterious	None	None	None	None	N
A/L	0.5401	ambiguous	0.5088	ambiguous	-0.339	Destabilizing	0.929	D	0.633	neutral	None	None	None	None	N
A/M	0.8069	likely_pathogenic	0.7858	pathogenic	-0.689	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
A/N	0.9884	likely_pathogenic	0.9855	pathogenic	-1.59	Destabilizing	0.998	D	0.873	deleterious	None	None	None	None	N
A/P	0.8899	likely_pathogenic	0.7903	pathogenic	-0.571	Destabilizing	0.998	D	0.835	deleterious	N	0.492711816	None	None	N
A/Q	0.9884	likely_pathogenic	0.9831	pathogenic	-1.654	Destabilizing	0.998	D	0.811	deleterious	None	None	None	None	N
A/R	0.9908	likely_pathogenic	0.9874	pathogenic	-1.157	Destabilizing	0.995	D	0.839	deleterious	None	None	None	None	N
A/S	0.4786	ambiguous	0.4581	ambiguous	-1.898	Destabilizing	0.976	D	0.747	deleterious	N	0.514663958	None	None	N
A/T	0.5901	likely_pathogenic	0.5858	pathogenic	-1.717	Destabilizing	0.952	D	0.742	deleterious	N	0.467579668	None	None	N
A/V	0.1937	likely_benign	0.2229	benign	-0.571	Destabilizing	0.125	N	0.402	neutral	N	0.506296151	None	None	N
A/W	0.9978	likely_pathogenic	0.9966	pathogenic	-1.561	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
A/Y	0.9909	likely_pathogenic	0.9872	pathogenic	-1.099	Destabilizing	0.998	D	0.857	deleterious	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.