TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16124	48595;48596;48597	chr2:178615731;178615730;178615729	chr2:179480458;179480457;179480456
N2AB	14483	43672;43673;43674	chr2:178615731;178615730;178615729	chr2:179480458;179480457;179480456
N2A	13556	40891;40892;40893	chr2:178615731;178615730;178615729	chr2:179480458;179480457;179480456
N2B	7059	21400;21401;21402	chr2:178615731;178615730;178615729	chr2:179480458;179480457;179480456
Novex-1	7184	21775;21776;21777	chr2:178615731;178615730;178615729	chr2:179480458;179480457;179480456
Novex-2	7251	21976;21977;21978	chr2:178615731;178615730;178615729	chr2:179480458;179480457;179480456
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-4
• Domain position: 70
• Structural Position: 103
• Q(SASA): 0.3973
• 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
E/K	rs754392831	-0.903	0.999	N	0.584	0.389	0.450441870249	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	1.68407E-04	None	0	None	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
E/A	0.235	likely_benign	0.2894	benign	-0.801	Destabilizing	0.999	D	0.704	prob.neutral	D	0.532176828	None	None	N
E/C	0.8954	likely_pathogenic	0.9254	pathogenic	-0.546	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
E/D	0.2511	likely_benign	0.3139	benign	-1.452	Destabilizing	0.999	D	0.463	neutral	N	0.474017555	None	None	N
E/F	0.8978	likely_pathogenic	0.9331	pathogenic	-0.142	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
E/G	0.3651	ambiguous	0.4474	ambiguous	-1.245	Destabilizing	1.0	D	0.775	deleterious	D	0.605935855	None	None	N
E/H	0.7574	likely_pathogenic	0.8422	pathogenic	-0.567	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	N
E/I	0.4808	ambiguous	0.5827	pathogenic	0.437	Stabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
E/K	0.4351	ambiguous	0.5587	ambiguous	-1.041	Destabilizing	0.999	D	0.584	neutral	N	0.49516215	None	None	N
E/L	0.6021	likely_pathogenic	0.7011	pathogenic	0.437	Stabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
E/M	0.5708	likely_pathogenic	0.6544	pathogenic	1.006	Stabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
E/N	0.4808	ambiguous	0.5908	pathogenic	-1.538	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
E/P	0.7401	likely_pathogenic	0.8108	pathogenic	0.046	Stabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/Q	0.2299	likely_benign	0.2901	benign	-1.284	Destabilizing	1.0	D	0.605	neutral	N	0.504799298	None	None	N
E/R	0.5939	likely_pathogenic	0.6981	pathogenic	-0.827	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
E/S	0.3538	ambiguous	0.4297	ambiguous	-1.972	Destabilizing	0.999	D	0.632	neutral	None	None	None	None	N
E/T	0.3286	likely_benign	0.4175	ambiguous	-1.59	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
E/V	0.2905	likely_benign	0.3672	ambiguous	0.046	Stabilizing	1.0	D	0.805	deleterious	N	0.471629816	None	None	N
E/W	0.9626	likely_pathogenic	0.9757	pathogenic	-0.017	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/Y	0.8024	likely_pathogenic	0.8628	pathogenic	0.077	Stabilizing	1.0	D	0.789	deleterious	None	None	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.