TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22565	67918;67919;67920	chr2:178579337;178579336;178579335	chr2:179444064;179444063;179444062
N2AB	20924	62995;62996;62997	chr2:178579337;178579336;178579335	chr2:179444064;179444063;179444062
N2A	19997	60214;60215;60216	chr2:178579337;178579336;178579335	chr2:179444064;179444063;179444062
N2B	13500	40723;40724;40725	chr2:178579337;178579336;178579335	chr2:179444064;179444063;179444062
Novex-1	13625	41098;41099;41100	chr2:178579337;178579336;178579335	chr2:179444064;179444063;179444062
Novex-2	13692	41299;41300;41301	chr2:178579337;178579336;178579335	chr2:179444064;179444063;179444062
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-127
• Domain position: 6
• Structural Position: 24
• Q(SASA): 0.6486
• 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
N/K	None	None	0.946	N	0.49	0.258	0.170165803431	gnomAD-4.0.0	6.87856E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	1.74764E-04	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
N/A	0.2913	likely_benign	0.2657	benign	-0.359	Destabilizing	0.702	D	0.557	neutral	None	None	None	None	I
N/C	0.3925	ambiguous	0.3446	ambiguous	0.421	Stabilizing	0.999	D	0.645	neutral	None	None	None	None	I
N/D	0.1448	likely_benign	0.1382	benign	-0.236	Destabilizing	0.946	D	0.455	neutral	N	0.450094231	None	None	I
N/E	0.4037	ambiguous	0.379	ambiguous	-0.277	Destabilizing	0.959	D	0.491	neutral	None	None	None	None	I
N/F	0.6336	likely_pathogenic	0.588	pathogenic	-0.737	Destabilizing	0.996	D	0.638	neutral	None	None	None	None	I
N/G	0.1638	likely_benign	0.1524	benign	-0.531	Destabilizing	0.005	N	0.251	neutral	None	None	None	None	I
N/H	0.129	likely_benign	0.1191	benign	-0.625	Destabilizing	0.995	D	0.532	neutral	N	0.485497671	None	None	I
N/I	0.4721	ambiguous	0.4206	ambiguous	0.007	Stabilizing	0.995	D	0.632	neutral	N	0.504526149	None	None	I
N/K	0.245	likely_benign	0.2198	benign	0.06	Stabilizing	0.946	D	0.49	neutral	N	0.46046594	None	None	I
N/L	0.4205	ambiguous	0.3925	ambiguous	0.007	Stabilizing	0.988	D	0.635	neutral	None	None	None	None	I
N/M	0.4459	ambiguous	0.4249	ambiguous	0.537	Stabilizing	0.999	D	0.618	neutral	None	None	None	None	I
N/P	0.9088	likely_pathogenic	0.8859	pathogenic	-0.089	Destabilizing	0.996	D	0.613	neutral	None	None	None	None	I
N/Q	0.3128	likely_benign	0.2842	benign	-0.454	Destabilizing	0.996	D	0.494	neutral	None	None	None	None	I
N/R	0.3484	ambiguous	0.2972	benign	0.176	Stabilizing	0.988	D	0.487	neutral	None	None	None	None	I
N/S	0.1288	likely_benign	0.1154	benign	-0.132	Destabilizing	0.78	D	0.468	neutral	N	0.43703172	None	None	I
N/T	0.2255	likely_benign	0.1987	benign	-0.041	Destabilizing	0.946	D	0.492	neutral	N	0.485324312	None	None	I
N/V	0.4607	ambiguous	0.419	ambiguous	-0.089	Destabilizing	0.988	D	0.623	neutral	None	None	None	None	I
N/W	0.815	likely_pathogenic	0.7968	pathogenic	-0.705	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	I
N/Y	0.1907	likely_benign	0.1661	benign	-0.446	Destabilizing	0.995	D	0.626	neutral	N	0.485671029	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.