TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6381	19366;19367;19368	chr2:178728897;178728896;178728895	chr2:179593624;179593623;179593622
N2AB	6064	18415;18416;18417	chr2:178728897;178728896;178728895	chr2:179593624;179593623;179593622
N2A	5137	15634;15635;15636	chr2:178728897;178728896;178728895	chr2:179593624;179593623;179593622
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-47
• Domain position: 90
• Structural Position: 177
• Q(SASA): 0.4219
• 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/E	rs983816997	-0.762	0.982	D	0.654	0.772	0.9051856181	gnomAD-2.1.1	4.21E-06	None	None	None	None	N	None	0	3.04E-05	None	0	0	None	0	None	0	0	0
V/E	rs983816997	-0.762	0.982	D	0.654	0.772	0.9051856181	gnomAD-4.0.0	6.93177E-07	None	None	None	None	N	None	0	2.3175E-05	None	0	0	None	0	0	0	0	0
V/I	None	None	0.863	N	0.575	0.486	0.783258508602	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	6.17284E-04	0	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	0.5746	likely_pathogenic	0.636	pathogenic	-1.863	Destabilizing	0.046	N	0.474	neutral	D	0.622000805	None	None	N
V/C	0.9374	likely_pathogenic	0.9489	pathogenic	-1.595	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
V/D	0.9808	likely_pathogenic	0.9902	pathogenic	-2.169	Highly Destabilizing	0.993	D	0.705	prob.neutral	None	None	None	None	N
V/E	0.9351	likely_pathogenic	0.9638	pathogenic	-2.116	Highly Destabilizing	0.982	D	0.654	neutral	D	0.65464494	None	None	N
V/F	0.7091	likely_pathogenic	0.8155	pathogenic	-1.382	Destabilizing	0.998	D	0.681	prob.neutral	None	None	None	None	N
V/G	0.7517	likely_pathogenic	0.8234	pathogenic	-2.218	Highly Destabilizing	0.964	D	0.67	neutral	D	0.65464494	None	None	N
V/H	0.9791	likely_pathogenic	0.9891	pathogenic	-1.66	Destabilizing	0.999	D	0.702	prob.neutral	None	None	None	None	N
V/I	0.1167	likely_benign	0.1045	benign	-0.952	Destabilizing	0.863	D	0.575	neutral	N	0.512498723	None	None	N
V/K	0.9532	likely_pathogenic	0.9744	pathogenic	-1.453	Destabilizing	0.986	D	0.658	neutral	None	None	None	None	N
V/L	0.5787	likely_pathogenic	0.6044	pathogenic	-0.952	Destabilizing	0.863	D	0.565	neutral	D	0.606981542	None	None	N
V/M	0.5833	likely_pathogenic	0.6465	pathogenic	-0.96	Destabilizing	0.998	D	0.706	prob.neutral	None	None	None	None	N
V/N	0.935	likely_pathogenic	0.9577	pathogenic	-1.44	Destabilizing	0.993	D	0.722	prob.delet.	None	None	None	None	N
V/P	0.8989	likely_pathogenic	0.9165	pathogenic	-1.225	Destabilizing	0.993	D	0.685	prob.neutral	None	None	None	None	N
V/Q	0.9203	likely_pathogenic	0.9554	pathogenic	-1.595	Destabilizing	0.993	D	0.697	prob.neutral	None	None	None	None	N
V/R	0.9247	likely_pathogenic	0.9605	pathogenic	-0.984	Destabilizing	0.993	D	0.722	prob.delet.	None	None	None	None	N
V/S	0.7859	likely_pathogenic	0.8432	pathogenic	-1.997	Destabilizing	0.973	D	0.629	neutral	None	None	None	None	N
V/T	0.6452	likely_pathogenic	0.6708	pathogenic	-1.835	Destabilizing	0.953	D	0.636	neutral	None	None	None	None	N
V/W	0.9899	likely_pathogenic	0.9953	pathogenic	-1.593	Destabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	N
V/Y	0.9621	likely_pathogenic	0.9823	pathogenic	-1.295	Destabilizing	0.998	D	0.687	prob.neutral	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.