TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23012	69259;69260;69261	chr2:178577301;178577300;178577299	chr2:179442028;179442027;179442026
N2AB	21371	64336;64337;64338	chr2:178577301;178577300;178577299	chr2:179442028;179442027;179442026
N2A	20444	61555;61556;61557	chr2:178577301;178577300;178577299	chr2:179442028;179442027;179442026
N2B	13947	42064;42065;42066	chr2:178577301;178577300;178577299	chr2:179442028;179442027;179442026
Novex-1	14072	42439;42440;42441	chr2:178577301;178577300;178577299	chr2:179442028;179442027;179442026
Novex-2	14139	42640;42641;42642	chr2:178577301;178577300;178577299	chr2:179442028;179442027;179442026
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-128
• Domain position: 63
• Structural Position: 146
• Q(SASA): 0.757
• 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
R/K	None	None	0.997	N	0.543	0.274	0.187945064343	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	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
R/A	0.9589	likely_pathogenic	0.9245	pathogenic	0.06	Stabilizing	0.999	D	0.596	neutral	None	None	None	None	I
R/C	0.7271	likely_pathogenic	0.5846	pathogenic	-0.162	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	I
R/D	0.9911	likely_pathogenic	0.9842	pathogenic	-0.18	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	I
R/E	0.9138	likely_pathogenic	0.8788	pathogenic	-0.126	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	I
R/F	0.9739	likely_pathogenic	0.9654	pathogenic	-0.2	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
R/G	0.937	likely_pathogenic	0.8761	pathogenic	-0.108	Destabilizing	1.0	D	0.57	neutral	N	0.484534018	None	None	I
R/H	0.5168	ambiguous	0.3871	ambiguous	-0.592	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
R/I	0.869	likely_pathogenic	0.8536	pathogenic	0.463	Stabilizing	1.0	D	0.729	prob.delet.	N	0.455451851	None	None	I
R/K	0.3697	ambiguous	0.2908	benign	-0.072	Destabilizing	0.997	D	0.543	neutral	N	0.49930589	None	None	I
R/L	0.8256	likely_pathogenic	0.7714	pathogenic	0.463	Stabilizing	1.0	D	0.57	neutral	None	None	None	None	I
R/M	0.9089	likely_pathogenic	0.8848	pathogenic	0.007	Stabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	I
R/N	0.9791	likely_pathogenic	0.9652	pathogenic	0.077	Stabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	I
R/P	0.9578	likely_pathogenic	0.9296	pathogenic	0.348	Stabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
R/Q	0.4469	ambiguous	0.3449	ambiguous	0.013	Stabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
R/S	0.9787	likely_pathogenic	0.9594	pathogenic	-0.174	Destabilizing	1.0	D	0.625	neutral	N	0.453312257	None	None	I
R/T	0.9459	likely_pathogenic	0.9112	pathogenic	-0.001	Destabilizing	1.0	D	0.623	neutral	N	0.458085197	None	None	I
R/V	0.9111	likely_pathogenic	0.8862	pathogenic	0.348	Stabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
R/W	0.7368	likely_pathogenic	0.6594	pathogenic	-0.327	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
R/Y	0.9324	likely_pathogenic	0.9023	pathogenic	0.085	Stabilizing	1.0	D	0.713	prob.delet.	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.