TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20082	60469;60470;60471	chr2:178591481;178591480;178591479	chr2:179456208;179456207;179456206
N2AB	18441	55546;55547;55548	chr2:178591481;178591480;178591479	chr2:179456208;179456207;179456206
N2A	17514	52765;52766;52767	chr2:178591481;178591480;178591479	chr2:179456208;179456207;179456206
N2B	11017	33274;33275;33276	chr2:178591481;178591480;178591479	chr2:179456208;179456207;179456206
Novex-1	11142	33649;33650;33651	chr2:178591481;178591480;178591479	chr2:179456208;179456207;179456206
Novex-2	11209	33850;33851;33852	chr2:178591481;178591480;178591479	chr2:179456208;179456207;179456206
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: Ig-120
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.15
• 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	None	None	0.928	D	0.753	0.356	0.715013705373	gnomAD-4.0.0	6.97569E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.06842E-07	0	0
V/G	None	None	0.864	N	0.721	0.38	0.723455425128	gnomAD-4.0.0	6.97572E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.23937E-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	0.4993	ambiguous	0.4359	ambiguous	-0.578	Destabilizing	0.024	N	0.343	neutral	N	0.482473221	None	None	N
V/C	0.9229	likely_pathogenic	0.9123	pathogenic	-0.644	Destabilizing	0.995	D	0.746	deleterious	None	None	None	None	N
V/D	0.898	likely_pathogenic	0.8086	pathogenic	-0.453	Destabilizing	0.945	D	0.795	deleterious	None	None	None	None	N
V/E	0.8309	likely_pathogenic	0.7337	pathogenic	-0.555	Destabilizing	0.928	D	0.753	deleterious	D	0.525378636	None	None	N
V/F	0.536	ambiguous	0.467	ambiguous	-0.711	Destabilizing	0.809	D	0.766	deleterious	None	None	None	None	N
V/G	0.6089	likely_pathogenic	0.5379	ambiguous	-0.733	Destabilizing	0.864	D	0.721	prob.delet.	N	0.501110785	None	None	N
V/H	0.9431	likely_pathogenic	0.9004	pathogenic	-0.26	Destabilizing	0.995	D	0.787	deleterious	None	None	None	None	N
V/I	0.1162	likely_benign	0.1193	benign	-0.31	Destabilizing	0.332	N	0.578	neutral	None	None	None	None	N
V/K	0.8632	likely_pathogenic	0.7652	pathogenic	-0.604	Destabilizing	0.945	D	0.749	deleterious	None	None	None	None	N
V/L	0.5325	ambiguous	0.5087	ambiguous	-0.31	Destabilizing	0.006	N	0.331	neutral	N	0.52018346	None	None	N
V/M	0.416	ambiguous	0.3819	ambiguous	-0.365	Destabilizing	0.864	D	0.673	neutral	N	0.501871254	None	None	N
V/N	0.8417	likely_pathogenic	0.7326	pathogenic	-0.34	Destabilizing	0.981	D	0.799	deleterious	None	None	None	None	N
V/P	0.753	likely_pathogenic	0.6205	pathogenic	-0.364	Destabilizing	0.945	D	0.774	deleterious	None	None	None	None	N
V/Q	0.8211	likely_pathogenic	0.7269	pathogenic	-0.577	Destabilizing	0.981	D	0.783	deleterious	None	None	None	None	N
V/R	0.8405	likely_pathogenic	0.7392	pathogenic	-0.049	Destabilizing	0.945	D	0.798	deleterious	None	None	None	None	N
V/S	0.6729	likely_pathogenic	0.5775	pathogenic	-0.701	Destabilizing	0.809	D	0.706	prob.neutral	None	None	None	None	N
V/T	0.5714	likely_pathogenic	0.5016	ambiguous	-0.703	Destabilizing	0.707	D	0.605	neutral	None	None	None	None	N
V/W	0.9623	likely_pathogenic	0.9473	pathogenic	-0.806	Destabilizing	0.995	D	0.755	deleterious	None	None	None	None	N
V/Y	0.8951	likely_pathogenic	0.8458	pathogenic	-0.517	Destabilizing	0.945	D	0.776	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.