TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28558	85897;85898;85899	chr2:178560460;178560459;178560458	chr2:179425187;179425186;179425185
N2AB	26917	80974;80975;80976	chr2:178560460;178560459;178560458	chr2:179425187;179425186;179425185
N2A	25990	78193;78194;78195	chr2:178560460;178560459;178560458	chr2:179425187;179425186;179425185
N2B	19493	58702;58703;58704	chr2:178560460;178560459;178560458	chr2:179425187;179425186;179425185
Novex-1	19618	59077;59078;59079	chr2:178560460;178560459;178560458	chr2:179425187;179425186;179425185
Novex-2	19685	59278;59279;59280	chr2:178560460;178560459;178560458	chr2:179425187;179425186;179425185
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-96
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.6053
• 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/A	None	None	0.989	N	0.637	0.457	0.376216005999	gnomAD-4.0.0	1.59197E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85865E-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
E/A	0.239	likely_benign	0.2035	benign	-0.446	Destabilizing	0.989	D	0.637	neutral	N	0.482307016	None	None	N
E/C	0.8443	likely_pathogenic	0.7923	pathogenic	0.023	Stabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/D	0.2126	likely_benign	0.194	benign	-0.42	Destabilizing	0.989	D	0.5	neutral	N	0.480914664	None	None	N
E/F	0.8038	likely_pathogenic	0.7239	pathogenic	-0.297	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
E/G	0.3352	likely_benign	0.2874	benign	-0.67	Destabilizing	0.998	D	0.707	prob.neutral	N	0.509565531	None	None	N
E/H	0.5001	ambiguous	0.4187	ambiguous	-0.223	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	N
E/I	0.3811	ambiguous	0.3019	benign	0.118	Stabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/K	0.2505	likely_benign	0.1905	benign	0.332	Stabilizing	0.978	D	0.532	neutral	N	0.493908431	None	None	N
E/L	0.4623	ambiguous	0.3727	ambiguous	0.118	Stabilizing	0.999	D	0.724	prob.delet.	None	None	None	None	N
E/M	0.4798	ambiguous	0.3996	ambiguous	0.313	Stabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
E/N	0.3599	ambiguous	0.2936	benign	-0.049	Destabilizing	0.999	D	0.663	neutral	None	None	None	None	N
E/P	0.9553	likely_pathogenic	0.9512	pathogenic	-0.049	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
E/Q	0.1407	likely_benign	0.1165	benign	0.003	Stabilizing	0.775	D	0.359	neutral	N	0.505992294	None	None	N
E/R	0.3649	ambiguous	0.2932	benign	0.473	Stabilizing	0.998	D	0.662	neutral	None	None	None	None	N
E/S	0.2826	likely_benign	0.2338	benign	-0.203	Destabilizing	0.992	D	0.582	neutral	None	None	None	None	N
E/T	0.2449	likely_benign	0.1958	benign	-0.016	Destabilizing	0.999	D	0.762	deleterious	None	None	None	None	N
E/V	0.2266	likely_benign	0.1839	benign	-0.049	Destabilizing	0.998	D	0.735	prob.delet.	N	0.466582618	None	None	N
E/W	0.9229	likely_pathogenic	0.8938	pathogenic	-0.128	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/Y	0.6951	likely_pathogenic	0.6159	pathogenic	-0.045	Destabilizing	1.0	D	0.787	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.