TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33585	100978;100979;100980	chr2:178535994;178535993;178535992	chr2:179400721;179400720;179400719
N2AB	31944	96055;96056;96057	chr2:178535994;178535993;178535992	chr2:179400721;179400720;179400719
N2A	31017	93274;93275;93276	chr2:178535994;178535993;178535992	chr2:179400721;179400720;179400719
N2B	24520	73783;73784;73785	chr2:178535994;178535993;178535992	chr2:179400721;179400720;179400719
Novex-1	24645	74158;74159;74160	chr2:178535994;178535993;178535992	chr2:179400721;179400720;179400719
Novex-2	24712	74359;74360;74361	chr2:178535994;178535993;178535992	chr2:179400721;179400720;179400719
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-158
• Domain position: 90
• Structural Position: 174
• Q(SASA): 0.095
• 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/W	rs1411829466	-2.053	1.0	D	0.837	0.826	0.902480430953	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	2.87687E-04	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	0.9801	likely_pathogenic	0.9755	pathogenic	-2.881	Highly Destabilizing	0.891	D	0.727	prob.delet.	None	None	None	None	N
L/C	0.9704	likely_pathogenic	0.9704	pathogenic	-2.419	Highly Destabilizing	0.998	D	0.767	deleterious	None	None	None	None	N
L/D	0.9998	likely_pathogenic	0.9997	pathogenic	-3.42	Highly Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	N
L/E	0.9985	likely_pathogenic	0.9974	pathogenic	-3.156	Highly Destabilizing	0.999	D	0.845	deleterious	None	None	None	None	N
L/F	0.8386	likely_pathogenic	0.806	pathogenic	-1.762	Destabilizing	0.034	N	0.45	neutral	D	0.595680452	None	None	N
L/G	0.9976	likely_pathogenic	0.996	pathogenic	-3.472	Highly Destabilizing	0.966	D	0.833	deleterious	None	None	None	None	N
L/H	0.9978	likely_pathogenic	0.9966	pathogenic	-2.948	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
L/I	0.1994	likely_benign	0.2049	benign	-1.141	Destabilizing	0.175	N	0.64	neutral	None	None	None	None	N
L/K	0.9975	likely_pathogenic	0.9951	pathogenic	-2.249	Highly Destabilizing	0.963	D	0.814	deleterious	None	None	None	None	N
L/M	0.4394	ambiguous	0.4284	ambiguous	-1.269	Destabilizing	0.837	D	0.701	prob.neutral	D	0.596084061	None	None	N
L/N	0.999	likely_pathogenic	0.9981	pathogenic	-2.748	Highly Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	N
L/P	0.9989	likely_pathogenic	0.998	pathogenic	-1.706	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
L/Q	0.9952	likely_pathogenic	0.9916	pathogenic	-2.548	Highly Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
L/R	0.9944	likely_pathogenic	0.9897	pathogenic	-2.006	Highly Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
L/S	0.9981	likely_pathogenic	0.9972	pathogenic	-3.456	Highly Destabilizing	0.922	D	0.636	neutral	D	0.642163385	None	None	N
L/T	0.9832	likely_pathogenic	0.9771	pathogenic	-3.032	Highly Destabilizing	0.987	D	0.772	deleterious	None	None	None	None	N
L/V	0.2544	likely_benign	0.28	benign	-1.706	Destabilizing	0.004	N	0.365	neutral	D	0.550556525	None	None	N
L/W	0.9919	likely_pathogenic	0.9878	pathogenic	-2.177	Highly Destabilizing	1.0	D	0.837	deleterious	D	0.642163385	None	None	N
L/Y	0.9944	likely_pathogenic	0.9926	pathogenic	-1.933	Destabilizing	0.976	D	0.792	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.