TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31299	94120;94121;94122	chr2:178547731;178547730;178547729	chr2:179412458;179412457;179412456
N2AB	29658	89197;89198;89199	chr2:178547731;178547730;178547729	chr2:179412458;179412457;179412456
N2A	28731	86416;86417;86418	chr2:178547731;178547730;178547729	chr2:179412458;179412457;179412456
N2B	22234	66925;66926;66927	chr2:178547731;178547730;178547729	chr2:179412458;179412457;179412456
Novex-1	22359	67300;67301;67302	chr2:178547731;178547730;178547729	chr2:179412458;179412457;179412456
Novex-2	22426	67501;67502;67503	chr2:178547731;178547730;178547729	chr2:179412458;179412457;179412456
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-151
• Domain position: 82
• Structural Position: 169
• Q(SASA): 0.5589
• 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/C	rs1321285611	-0.774	1.0	N	0.833	0.515	0.832015162006	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
F/L	None	None	0.999	N	0.59	0.427	0.549164311151	gnomAD-4.0.0	1.59105E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85778E-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	0.7904	likely_pathogenic	0.8038	pathogenic	-1.535	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	I
F/C	0.5269	ambiguous	0.5384	ambiguous	-0.924	Destabilizing	1.0	D	0.833	deleterious	N	0.474240527	None	None	I
F/D	0.9594	likely_pathogenic	0.9685	pathogenic	0.484	Stabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
F/E	0.9519	likely_pathogenic	0.9602	pathogenic	0.526	Stabilizing	1.0	D	0.826	deleterious	None	None	None	None	I
F/G	0.9392	likely_pathogenic	0.9455	pathogenic	-1.804	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
F/H	0.7924	likely_pathogenic	0.8034	pathogenic	-0.134	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
F/I	0.4025	ambiguous	0.4366	ambiguous	-0.78	Destabilizing	1.0	D	0.761	deleterious	N	0.484110804	None	None	I
F/K	0.966	likely_pathogenic	0.969	pathogenic	-0.677	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
F/L	0.9312	likely_pathogenic	0.9401	pathogenic	-0.78	Destabilizing	0.999	D	0.59	neutral	N	0.447747359	None	None	I
F/M	0.7234	likely_pathogenic	0.7413	pathogenic	-0.69	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
F/N	0.9067	likely_pathogenic	0.9147	pathogenic	-0.715	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
F/P	0.9987	likely_pathogenic	0.9991	pathogenic	-1.017	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
F/Q	0.9255	likely_pathogenic	0.9356	pathogenic	-0.718	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
F/R	0.9307	likely_pathogenic	0.936	pathogenic	-0.137	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	I
F/S	0.7484	likely_pathogenic	0.7652	pathogenic	-1.552	Destabilizing	1.0	D	0.849	deleterious	N	0.456961488	None	None	I
F/T	0.8043	likely_pathogenic	0.8202	pathogenic	-1.412	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
F/V	0.35	ambiguous	0.3781	ambiguous	-1.017	Destabilizing	1.0	D	0.789	deleterious	N	0.452441103	None	None	I
F/W	0.7321	likely_pathogenic	0.7524	pathogenic	-0.171	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
F/Y	0.2629	likely_benign	0.2656	benign	-0.328	Destabilizing	0.999	D	0.555	neutral	N	0.518300735	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.