TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23605	71038;71039;71040	chr2:178575319;178575318;178575317	chr2:179440046;179440045;179440044
N2AB	21964	66115;66116;66117	chr2:178575319;178575318;178575317	chr2:179440046;179440045;179440044
N2A	21037	63334;63335;63336	chr2:178575319;178575318;178575317	chr2:179440046;179440045;179440044
N2B	14540	43843;43844;43845	chr2:178575319;178575318;178575317	chr2:179440046;179440045;179440044
Novex-1	14665	44218;44219;44220	chr2:178575319;178575318;178575317	chr2:179440046;179440045;179440044
Novex-2	14732	44419;44420;44421	chr2:178575319;178575318;178575317	chr2:179440046;179440045;179440044
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-59
• Domain position: 74
• Structural Position: 108
• Q(SASA): 0.0826
• 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/L	rs368325616	None	0.853	D	0.381	0.506	0.739614512186	gnomAD-4.0.0	1.98455E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.51875E-05	0	1.65678E-05
V/M	None	None	0.999	D	0.652	0.606	0.826566672349	gnomAD-4.0.0	6.84329E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99554E-07	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	0.8895	likely_pathogenic	0.8878	pathogenic	-2.738	Highly Destabilizing	0.987	D	0.622	neutral	D	0.556923213	None	None	N
V/C	0.972	likely_pathogenic	0.9757	pathogenic	-2.235	Highly Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
V/D	0.9978	likely_pathogenic	0.9979	pathogenic	-3.437	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/E	0.9936	likely_pathogenic	0.9934	pathogenic	-3.157	Highly Destabilizing	1.0	D	0.847	deleterious	D	0.64666385	None	None	N
V/F	0.9548	likely_pathogenic	0.9535	pathogenic	-1.429	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
V/G	0.9373	likely_pathogenic	0.935	pathogenic	-3.249	Highly Destabilizing	1.0	D	0.865	deleterious	D	0.64666385	None	None	N
V/H	0.9989	likely_pathogenic	0.999	pathogenic	-2.879	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
V/I	0.1228	likely_benign	0.1202	benign	-1.228	Destabilizing	0.351	N	0.235	neutral	None	None	None	None	N
V/K	0.9961	likely_pathogenic	0.9964	pathogenic	-2.256	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
V/L	0.7707	likely_pathogenic	0.7673	pathogenic	-1.228	Destabilizing	0.853	D	0.381	neutral	D	0.526369335	None	None	N
V/M	0.8528	likely_pathogenic	0.8487	pathogenic	-1.586	Destabilizing	0.999	D	0.652	neutral	D	0.534299508	None	None	N
V/N	0.993	likely_pathogenic	0.9932	pathogenic	-2.827	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
V/P	0.9968	likely_pathogenic	0.9969	pathogenic	-1.72	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
V/Q	0.9948	likely_pathogenic	0.9951	pathogenic	-2.523	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
V/R	0.9922	likely_pathogenic	0.9928	pathogenic	-2.169	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
V/S	0.9781	likely_pathogenic	0.9785	pathogenic	-3.301	Highly Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
V/T	0.948	likely_pathogenic	0.9493	pathogenic	-2.898	Highly Destabilizing	1.0	D	0.613	neutral	None	None	None	None	N
V/W	0.9994	likely_pathogenic	0.9994	pathogenic	-1.902	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
V/Y	0.9946	likely_pathogenic	0.9947	pathogenic	-1.765	Destabilizing	1.0	D	0.717	prob.delet.	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.