TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13699	41320;41321;41322	chr2:178636632;178636631;178636630	chr2:179501359;179501358;179501357
N2AB	12058	36397;36398;36399	chr2:178636632;178636631;178636630	chr2:179501359;179501358;179501357
N2A	11131	33616;33617;33618	chr2:178636632;178636631;178636630	chr2:179501359;179501358;179501357
N2B	4634	14125;14126;14127	chr2:178636632;178636631;178636630	chr2:179501359;179501358;179501357
Novex-1	4759	14500;14501;14502	chr2:178636632;178636631;178636630	chr2:179501359;179501358;179501357
Novex-2	4826	14701;14702;14703	chr2:178636632;178636631;178636630	chr2:179501359;179501358;179501357
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-87
• Domain position: 16
• Structural Position: 22
• Q(SASA): 0.9954
• 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
F/I	None	None	0.024	N	0.263	0.173	0.245660935333	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-05	0
F/L	None	None	0.01	N	0.222	0.168	0.0482279557977	gnomAD-4.0.0	1.36874E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79922E-06	0	0
F/S	None	None	None	N	0.171	0.152	0.227934060464	gnomAD-4.0.0	1.36872E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79922E-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
F/A	0.2074	likely_benign	0.1494	benign	-2.559	Highly Destabilizing	0.003	N	0.197	neutral	None	None	None	None	I
F/C	0.5185	ambiguous	0.3059	benign	-1.836	Destabilizing	0.295	N	0.309	neutral	N	0.451421669	None	None	I
F/D	0.6538	likely_pathogenic	0.6477	pathogenic	-1.602	Destabilizing	0.016	N	0.333	neutral	None	None	None	None	I
F/E	0.7164	likely_pathogenic	0.6846	pathogenic	-1.46	Destabilizing	0.007	N	0.345	neutral	None	None	None	None	I
F/G	0.4958	ambiguous	0.4484	ambiguous	-2.939	Highly Destabilizing	0.003	N	0.267	neutral	None	None	None	None	I
F/H	0.5516	ambiguous	0.5406	ambiguous	-1.271	Destabilizing	0.356	N	0.295	neutral	None	None	None	None	I
F/I	0.2819	likely_benign	0.1935	benign	-1.375	Destabilizing	0.024	N	0.263	neutral	N	0.416316826	None	None	I
F/K	0.7829	likely_pathogenic	0.8012	pathogenic	-1.577	Destabilizing	0.016	N	0.342	neutral	None	None	None	None	I
F/L	0.8223	likely_pathogenic	0.7641	pathogenic	-1.375	Destabilizing	0.01	N	0.222	neutral	N	0.423262637	None	None	I
F/M	0.4145	ambiguous	0.3493	ambiguous	-1.298	Destabilizing	0.628	D	0.251	neutral	None	None	None	None	I
F/N	0.3313	likely_benign	0.3031	benign	-1.713	Destabilizing	0.016	N	0.328	neutral	None	None	None	None	I
F/P	0.9472	likely_pathogenic	0.8679	pathogenic	-1.77	Destabilizing	0.072	N	0.373	neutral	None	None	None	None	I
F/Q	0.6721	likely_pathogenic	0.6475	pathogenic	-1.764	Destabilizing	0.072	N	0.377	neutral	None	None	None	None	I
F/R	0.7639	likely_pathogenic	0.7588	pathogenic	-0.978	Destabilizing	0.072	N	0.375	neutral	None	None	None	None	I
F/S	0.1558	likely_benign	0.115	benign	-2.585	Highly Destabilizing	None	N	0.171	neutral	N	0.397851314	None	None	I
F/T	0.2216	likely_benign	0.1597	benign	-2.343	Highly Destabilizing	0.007	N	0.258	neutral	None	None	None	None	I
F/V	0.2241	likely_benign	0.1568	benign	-1.77	Destabilizing	0.024	N	0.307	neutral	N	0.39651831	None	None	I
F/W	0.5648	likely_pathogenic	0.5782	pathogenic	-0.351	Destabilizing	0.628	D	0.305	neutral	None	None	None	None	I
F/Y	0.1671	likely_benign	0.1652	benign	-0.623	Destabilizing	0.047	N	0.335	neutral	N	0.420138764	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.