TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30007	90244;90245;90246	chr2:178552881;178552880;178552879	chr2:179417608;179417607;179417606
N2AB	28366	85321;85322;85323	chr2:178552881;178552880;178552879	chr2:179417608;179417607;179417606
N2A	27439	82540;82541;82542	chr2:178552881;178552880;178552879	chr2:179417608;179417607;179417606
N2B	20942	63049;63050;63051	chr2:178552881;178552880;178552879	chr2:179417608;179417607;179417606
Novex-1	21067	63424;63425;63426	chr2:178552881;178552880;178552879	chr2:179417608;179417607;179417606
Novex-2	21134	63625;63626;63627	chr2:178552881;178552880;178552879	chr2:179417608;179417607;179417606
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: Fn3-106
• Domain position: 75
• Structural Position: 108
• Q(SASA): 0.0664
• 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/A	None	None	0.999	D	0.624	0.803	0.815397466254	gnomAD-4.0.0	1.5913E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43279E-05	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	0.927	likely_pathogenic	0.9222	pathogenic	-2.694	Highly Destabilizing	0.999	D	0.624	neutral	D	0.565481588	None	None	N
V/C	0.9766	likely_pathogenic	0.9754	pathogenic	-2.171	Highly Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
V/D	0.9986	likely_pathogenic	0.9988	pathogenic	-3.694	Highly Destabilizing	1.0	D	0.893	deleterious	D	0.652003637	None	None	N
V/E	0.9956	likely_pathogenic	0.9962	pathogenic	-3.393	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
V/F	0.9188	likely_pathogenic	0.9221	pathogenic	-1.578	Destabilizing	1.0	D	0.817	deleterious	D	0.572064953	None	None	N
V/G	0.9494	likely_pathogenic	0.9503	pathogenic	-3.255	Highly Destabilizing	1.0	D	0.885	deleterious	D	0.652003637	None	None	N
V/H	0.9986	likely_pathogenic	0.9987	pathogenic	-3.034	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/I	0.1097	likely_benign	0.1071	benign	-1.044	Destabilizing	0.997	D	0.608	neutral	N	0.492132153	None	None	N
V/K	0.9961	likely_pathogenic	0.9966	pathogenic	-2.361	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
V/L	0.7412	likely_pathogenic	0.7203	pathogenic	-1.044	Destabilizing	0.997	D	0.639	neutral	D	0.531965195	None	None	N
V/M	0.8451	likely_pathogenic	0.8396	pathogenic	-1.277	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
V/N	0.9942	likely_pathogenic	0.9945	pathogenic	-3.01	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
V/P	0.9959	likely_pathogenic	0.9961	pathogenic	-1.58	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
V/Q	0.995	likely_pathogenic	0.9953	pathogenic	-2.698	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
V/R	0.9926	likely_pathogenic	0.9933	pathogenic	-2.3	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
V/S	0.9814	likely_pathogenic	0.9816	pathogenic	-3.491	Highly Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
V/T	0.9564	likely_pathogenic	0.9567	pathogenic	-3.05	Highly Destabilizing	0.999	D	0.664	neutral	None	None	None	None	N
V/W	0.9992	likely_pathogenic	0.9992	pathogenic	-2.137	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
V/Y	0.993	likely_pathogenic	0.9934	pathogenic	-1.893	Destabilizing	1.0	D	0.819	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.