TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20345	61258;61259;61260	chr2:178590692;178590691;178590690	chr2:179455419;179455418;179455417
N2AB	18704	56335;56336;56337	chr2:178590692;178590691;178590690	chr2:179455419;179455418;179455417
N2A	17777	53554;53555;53556	chr2:178590692;178590691;178590690	chr2:179455419;179455418;179455417
N2B	11280	34063;34064;34065	chr2:178590692;178590691;178590690	chr2:179455419;179455418;179455417
Novex-1	11405	34438;34439;34440	chr2:178590692;178590691;178590690	chr2:179455419;179455418;179455417
Novex-2	11472	34639;34640;34641	chr2:178590692;178590691;178590690	chr2:179455419;179455418;179455417
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: Fn3-35
• Domain position: 75
• Structural Position: 108
• Q(SASA): 0.0716
• 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/D	None	None	0.991	D	0.889	0.724	0.790947836327	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.5231	ambiguous	0.5616	ambiguous	-2.695	Highly Destabilizing	0.046	N	0.306	neutral	D	0.541452304	None	None	N
V/C	0.8749	likely_pathogenic	0.8835	pathogenic	-2.174	Highly Destabilizing	0.998	D	0.78	deleterious	None	None	None	None	N
V/D	0.994	likely_pathogenic	0.9923	pathogenic	-3.395	Highly Destabilizing	0.991	D	0.889	deleterious	D	0.645967356	None	None	N
V/E	0.9894	likely_pathogenic	0.9863	pathogenic	-3.103	Highly Destabilizing	0.986	D	0.849	deleterious	None	None	None	None	N
V/F	0.8295	likely_pathogenic	0.8291	pathogenic	-1.343	Destabilizing	0.991	D	0.781	deleterious	D	0.579306655	None	None	N
V/G	0.7872	likely_pathogenic	0.7703	pathogenic	-3.233	Highly Destabilizing	0.964	D	0.832	deleterious	D	0.645967356	None	None	N
V/H	0.9963	likely_pathogenic	0.9956	pathogenic	-2.898	Highly Destabilizing	0.999	D	0.892	deleterious	None	None	None	None	N
V/I	0.1037	likely_benign	0.1124	benign	-1.105	Destabilizing	0.863	D	0.547	neutral	D	0.536622711	None	None	N
V/K	0.995	likely_pathogenic	0.9928	pathogenic	-2.128	Highly Destabilizing	0.986	D	0.849	deleterious	None	None	None	None	N
V/L	0.5664	likely_pathogenic	0.5853	pathogenic	-1.105	Destabilizing	0.863	D	0.612	neutral	D	0.522913068	None	None	N
V/M	0.6099	likely_pathogenic	0.6497	pathogenic	-1.479	Destabilizing	0.998	D	0.695	prob.neutral	None	None	None	None	N
V/N	0.9698	likely_pathogenic	0.9661	pathogenic	-2.73	Highly Destabilizing	0.993	D	0.905	deleterious	None	None	None	None	N
V/P	0.9907	likely_pathogenic	0.9863	pathogenic	-1.622	Destabilizing	0.993	D	0.867	deleterious	None	None	None	None	N
V/Q	0.9873	likely_pathogenic	0.9844	pathogenic	-2.398	Highly Destabilizing	0.993	D	0.885	deleterious	None	None	None	None	N
V/R	0.9889	likely_pathogenic	0.9836	pathogenic	-2.113	Highly Destabilizing	0.993	D	0.903	deleterious	None	None	None	None	N
V/S	0.8271	likely_pathogenic	0.8343	pathogenic	-3.217	Highly Destabilizing	0.973	D	0.817	deleterious	None	None	None	None	N
V/T	0.6582	likely_pathogenic	0.7296	pathogenic	-2.793	Highly Destabilizing	0.953	D	0.631	neutral	None	None	None	None	N
V/W	0.9978	likely_pathogenic	0.9975	pathogenic	-1.836	Destabilizing	0.999	D	0.859	deleterious	None	None	None	None	N
V/Y	0.9842	likely_pathogenic	0.9816	pathogenic	-1.692	Destabilizing	0.998	D	0.789	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.