TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20282	61069;61070;61071	chr2:178590881;178590880;178590879	chr2:179455608;179455607;179455606
N2AB	18641	56146;56147;56148	chr2:178590881;178590880;178590879	chr2:179455608;179455607;179455606
N2A	17714	53365;53366;53367	chr2:178590881;178590880;178590879	chr2:179455608;179455607;179455606
N2B	11217	33874;33875;33876	chr2:178590881;178590880;178590879	chr2:179455608;179455607;179455606
Novex-1	11342	34249;34250;34251	chr2:178590881;178590880;178590879	chr2:179455608;179455607;179455606
Novex-2	11409	34450;34451;34452	chr2:178590881;178590880;178590879	chr2:179455608;179455607;179455606
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-35
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.5304
• 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
D/E	None	None	1.0	N	0.387	0.307	0.19670166235	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
D/A	0.2976	likely_benign	0.334	benign	-0.194	Destabilizing	1.0	D	0.679	prob.neutral	N	0.482520789	None	None	N
D/C	0.7865	likely_pathogenic	0.8091	pathogenic	0.191	Stabilizing	1.0	D	0.604	neutral	None	None	None	None	N
D/E	0.242	likely_benign	0.2728	benign	-0.254	Destabilizing	1.0	D	0.387	neutral	N	0.48121128	None	None	N
D/F	0.8187	likely_pathogenic	0.8536	pathogenic	-0.256	Destabilizing	1.0	D	0.626	neutral	None	None	None	None	N
D/G	0.2953	likely_benign	0.3428	ambiguous	-0.371	Destabilizing	1.0	D	0.693	prob.neutral	D	0.524964844	None	None	N
D/H	0.5518	ambiguous	0.6052	pathogenic	-0.126	Destabilizing	1.0	D	0.592	neutral	N	0.483614144	None	None	N
D/I	0.7152	likely_pathogenic	0.7609	pathogenic	0.215	Stabilizing	1.0	D	0.663	neutral	None	None	None	None	N
D/K	0.7141	likely_pathogenic	0.7599	pathogenic	0.466	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
D/L	0.6674	likely_pathogenic	0.7101	pathogenic	0.215	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
D/M	0.7969	likely_pathogenic	0.8291	pathogenic	0.374	Stabilizing	1.0	D	0.603	neutral	None	None	None	None	N
D/N	0.1572	likely_benign	0.1754	benign	0.223	Stabilizing	1.0	D	0.631	neutral	N	0.4662819	None	None	N
D/P	0.9774	likely_pathogenic	0.9797	pathogenic	0.1	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
D/Q	0.5918	likely_pathogenic	0.6532	pathogenic	0.236	Stabilizing	1.0	D	0.674	neutral	None	None	None	None	N
D/R	0.735	likely_pathogenic	0.7791	pathogenic	0.545	Stabilizing	1.0	D	0.649	neutral	None	None	None	None	N
D/S	0.2143	likely_benign	0.2412	benign	0.123	Stabilizing	1.0	D	0.657	neutral	None	None	None	None	N
D/T	0.4742	ambiguous	0.5416	ambiguous	0.259	Stabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
D/V	0.4875	ambiguous	0.5405	ambiguous	0.1	Stabilizing	1.0	D	0.7	prob.neutral	N	0.480536271	None	None	N
D/W	0.9609	likely_pathogenic	0.9672	pathogenic	-0.166	Destabilizing	1.0	D	0.615	neutral	None	None	None	None	N
D/Y	0.4688	ambiguous	0.5186	ambiguous	-0.022	Destabilizing	1.0	D	0.604	neutral	N	0.493324608	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.