TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20537	61834;61835;61836	chr2:178590116;178590115;178590114	chr2:179454843;179454842;179454841
N2AB	18896	56911;56912;56913	chr2:178590116;178590115;178590114	chr2:179454843;179454842;179454841
N2A	17969	54130;54131;54132	chr2:178590116;178590115;178590114	chr2:179454843;179454842;179454841
N2B	11472	34639;34640;34641	chr2:178590116;178590115;178590114	chr2:179454843;179454842;179454841
Novex-1	11597	35014;35015;35016	chr2:178590116;178590115;178590114	chr2:179454843;179454842;179454841
Novex-2	11664	35215;35216;35217	chr2:178590116;178590115;178590114	chr2:179454843;179454842;179454841
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-121
• Domain position: 59
• Structural Position: 141
• Q(SASA): 0.4962
• 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
K/E	None	None	0.999	N	0.565	0.402	0.391000631824	gnomAD-4.0.0	3.1848E-06	None	None	None	None	I	None	1.13289E-04	0	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
K/A	0.534	ambiguous	0.5244	ambiguous	-0.394	Destabilizing	0.999	D	0.606	neutral	None	None	None	None	I
K/C	0.7894	likely_pathogenic	0.7472	pathogenic	-0.523	Destabilizing	1.0	D	0.601	neutral	None	None	None	None	I
K/D	0.7591	likely_pathogenic	0.7699	pathogenic	-0.305	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	I
K/E	0.3247	likely_benign	0.3354	benign	-0.239	Destabilizing	0.999	D	0.565	neutral	N	0.493154362	None	None	I
K/F	0.8895	likely_pathogenic	0.8603	pathogenic	-0.335	Destabilizing	1.0	D	0.611	neutral	None	None	None	None	I
K/G	0.6094	likely_pathogenic	0.6113	pathogenic	-0.715	Destabilizing	1.0	D	0.63	neutral	None	None	None	None	I
K/H	0.3889	ambiguous	0.3708	ambiguous	-1.149	Destabilizing	1.0	D	0.535	neutral	None	None	None	None	I
K/I	0.6176	likely_pathogenic	0.5629	ambiguous	0.413	Stabilizing	1.0	D	0.662	neutral	D	0.534926413	None	None	I
K/L	0.5501	ambiguous	0.5132	ambiguous	0.413	Stabilizing	1.0	D	0.63	neutral	None	None	None	None	I
K/M	0.4351	ambiguous	0.391	ambiguous	0.427	Stabilizing	1.0	D	0.525	neutral	None	None	None	None	I
K/N	0.6083	likely_pathogenic	0.6056	pathogenic	-0.312	Destabilizing	1.0	D	0.625	neutral	N	0.510452043	None	None	I
K/P	0.7442	likely_pathogenic	0.771	pathogenic	0.175	Stabilizing	1.0	D	0.609	neutral	None	None	None	None	I
K/Q	0.1824	likely_benign	0.1814	benign	-0.52	Destabilizing	1.0	D	0.606	neutral	N	0.476472756	None	None	I
K/R	0.0857	likely_benign	0.0855	benign	-0.464	Destabilizing	0.999	D	0.494	neutral	N	0.494039796	None	None	I
K/S	0.5929	likely_pathogenic	0.5889	pathogenic	-0.924	Destabilizing	0.999	D	0.58	neutral	None	None	None	None	I
K/T	0.3026	likely_benign	0.2794	benign	-0.67	Destabilizing	1.0	D	0.643	neutral	N	0.493309077	None	None	I
K/V	0.565	likely_pathogenic	0.5146	ambiguous	0.175	Stabilizing	1.0	D	0.655	neutral	None	None	None	None	I
K/W	0.8361	likely_pathogenic	0.7919	pathogenic	-0.217	Destabilizing	1.0	D	0.608	neutral	None	None	None	None	I
K/Y	0.7957	likely_pathogenic	0.7619	pathogenic	0.122	Stabilizing	1.0	D	0.593	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.