TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17492	52699;52700;52701	chr2:178608409;178608408;178608407	chr2:179473136;179473135;179473134
N2AB	15851	47776;47777;47778	chr2:178608409;178608408;178608407	chr2:179473136;179473135;179473134
N2A	14924	44995;44996;44997	chr2:178608409;178608408;178608407	chr2:179473136;179473135;179473134
N2B	8427	25504;25505;25506	chr2:178608409;178608408;178608407	chr2:179473136;179473135;179473134
Novex-1	8552	25879;25880;25881	chr2:178608409;178608408;178608407	chr2:179473136;179473135;179473134
Novex-2	8619	26080;26081;26082	chr2:178608409;178608408;178608407	chr2:179473136;179473135;179473134
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-15
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.5017
• 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
N/D	None	None	0.896	N	0.521	0.205	0.187945064343	gnomAD-4.0.0	1.60022E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.44421E-05	0
N/K	rs769123120	-0.095	0.026	N	0.217	0.127	0.0954503805726	gnomAD-2.1.1	1.24E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.00496E-04	None	0	0	0
N/K	rs769123120	-0.095	0.026	N	0.217	0.127	0.0954503805726	gnomAD-4.0.0	3.42926E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00831E-07	3.50034E-05	1.66041E-05

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
N/A	0.1708	likely_benign	0.1727	benign	-0.575	Destabilizing	0.919	D	0.628	neutral	None	None	None	None	N
N/C	0.2431	likely_benign	0.2479	benign	0.085	Stabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
N/D	0.1467	likely_benign	0.1447	benign	-0.208	Destabilizing	0.896	D	0.521	neutral	N	0.430206456	None	None	N
N/E	0.191	likely_benign	0.2081	benign	-0.151	Destabilizing	0.851	D	0.446	neutral	None	None	None	None	N
N/F	0.4643	ambiguous	0.4783	ambiguous	-0.579	Destabilizing	0.976	D	0.777	deleterious	None	None	None	None	N
N/G	0.2731	likely_benign	0.2715	benign	-0.853	Destabilizing	0.919	D	0.463	neutral	None	None	None	None	N
N/H	0.1013	likely_benign	0.1039	benign	-0.727	Destabilizing	0.995	D	0.589	neutral	N	0.442541035	None	None	N
N/I	0.1773	likely_benign	0.1774	benign	0.104	Stabilizing	0.938	D	0.731	prob.delet.	N	0.459337285	None	None	N
N/K	0.1501	likely_benign	0.1564	benign	-0.244	Destabilizing	0.026	N	0.217	neutral	N	0.386876967	None	None	N
N/L	0.1893	likely_benign	0.1926	benign	0.104	Stabilizing	0.034	N	0.483	neutral	None	None	None	None	N
N/M	0.2255	likely_benign	0.229	benign	0.234	Stabilizing	0.993	D	0.772	deleterious	None	None	None	None	N
N/P	0.7248	likely_pathogenic	0.7099	pathogenic	-0.094	Destabilizing	0.988	D	0.775	deleterious	None	None	None	None	N
N/Q	0.1918	likely_benign	0.2077	benign	-0.606	Destabilizing	0.976	D	0.573	neutral	None	None	None	None	N
N/R	0.1894	likely_benign	0.1996	benign	-0.295	Destabilizing	0.851	D	0.519	neutral	None	None	None	None	N
N/S	0.0963	likely_benign	0.0956	benign	-0.592	Destabilizing	0.896	D	0.479	neutral	N	0.414735572	None	None	N
N/T	0.1095	likely_benign	0.1081	benign	-0.364	Destabilizing	0.896	D	0.505	neutral	N	0.393168221	None	None	N
N/V	0.1762	likely_benign	0.1788	benign	-0.094	Destabilizing	0.851	D	0.691	prob.neutral	None	None	None	None	N
N/W	0.6505	likely_pathogenic	0.6733	pathogenic	-0.505	Destabilizing	0.999	D	0.756	deleterious	None	None	None	None	N
N/Y	0.1567	likely_benign	0.165	benign	-0.265	Destabilizing	0.995	D	0.775	deleterious	N	0.451333877	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.