TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18074	54445;54446;54447	chr2:178604869;178604868;178604867	chr2:179469596;179469595;179469594
N2AB	16433	49522;49523;49524	chr2:178604869;178604868;178604867	chr2:179469596;179469595;179469594
N2A	15506	46741;46742;46743	chr2:178604869;178604868;178604867	chr2:179469596;179469595;179469594
N2B	9009	27250;27251;27252	chr2:178604869;178604868;178604867	chr2:179469596;179469595;179469594
Novex-1	9134	27625;27626;27627	chr2:178604869;178604868;178604867	chr2:179469596;179469595;179469594
Novex-2	9201	27826;27827;27828	chr2:178604869;178604868;178604867	chr2:179469596;179469595;179469594
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-19
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.3075
• 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
V/G	None	None	1.0	N	0.845	0.593	0.80329002814	gnomAD-4.0.0	1.59487E-06	None	None	None	None	N	None	5.67924E-05	0	None	0	0	None	0	0	0	0	0
V/L	None	None	0.997	N	0.616	0.348	0.556145022309	gnomAD-4.0.0	1.59493E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86425E-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
V/A	0.616	likely_pathogenic	0.6197	pathogenic	-1.579	Destabilizing	0.999	D	0.625	neutral	N	0.482752862	None	None	N
V/C	0.9041	likely_pathogenic	0.9017	pathogenic	-1.227	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
V/D	0.9867	likely_pathogenic	0.9864	pathogenic	-1.26	Destabilizing	1.0	D	0.864	deleterious	D	0.522841756	None	None	N
V/E	0.9701	likely_pathogenic	0.9673	pathogenic	-1.166	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
V/F	0.403	ambiguous	0.4758	ambiguous	-1.03	Destabilizing	1.0	D	0.845	deleterious	D	0.526698427	None	None	N
V/G	0.8688	likely_pathogenic	0.8638	pathogenic	-2.008	Highly Destabilizing	1.0	D	0.845	deleterious	N	0.498950603	None	None	N
V/H	0.9833	likely_pathogenic	0.9823	pathogenic	-1.65	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
V/I	0.0762	likely_benign	0.0819	benign	-0.461	Destabilizing	0.997	D	0.598	neutral	N	0.470749144	None	None	N
V/K	0.9694	likely_pathogenic	0.9655	pathogenic	-1.274	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
V/L	0.4643	ambiguous	0.5008	ambiguous	-0.461	Destabilizing	0.997	D	0.616	neutral	N	0.495164799	None	None	N
V/M	0.4081	ambiguous	0.4415	ambiguous	-0.47	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
V/N	0.953	likely_pathogenic	0.953	pathogenic	-1.218	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
V/P	0.7714	likely_pathogenic	0.8207	pathogenic	-0.799	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
V/Q	0.9626	likely_pathogenic	0.9582	pathogenic	-1.213	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/R	0.9581	likely_pathogenic	0.9531	pathogenic	-1.0	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
V/S	0.8807	likely_pathogenic	0.8708	pathogenic	-1.869	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
V/T	0.7677	likely_pathogenic	0.7511	pathogenic	-1.633	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
V/W	0.9765	likely_pathogenic	0.98	pathogenic	-1.321	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
V/Y	0.9218	likely_pathogenic	0.9307	pathogenic	-0.973	Destabilizing	1.0	D	0.849	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.