TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32495	97708;97709;97710	chr2:178542273;178542272;178542271	chr2:179407000;179406999;179406998
N2AB	30854	92785;92786;92787	chr2:178542273;178542272;178542271	chr2:179407000;179406999;179406998
N2A	29927	90004;90005;90006	chr2:178542273;178542272;178542271	chr2:179407000;179406999;179406998
N2B	23430	70513;70514;70515	chr2:178542273;178542272;178542271	chr2:179407000;179406999;179406998
Novex-1	23555	70888;70889;70890	chr2:178542273;178542272;178542271	chr2:179407000;179406999;179406998
Novex-2	23622	71089;71090;71091	chr2:178542273;178542272;178542271	chr2:179407000;179406999;179406998
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-124
• Domain position: 97
• Structural Position: 132
• Q(SASA): 0.6975
• 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
S/G	rs1328086725	-0.875	0.997	N	0.53	0.227	0.395894371353	gnomAD-2.1.1	4.14E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.17E-06	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
S/A	0.2008	likely_benign	0.1708	benign	-0.206	Destabilizing	0.995	D	0.513	neutral	None	None	None	None	N
S/C	0.3594	ambiguous	0.2833	benign	-0.203	Destabilizing	1.0	D	0.725	deleterious	N	0.521858329	None	None	N
S/D	0.6471	likely_pathogenic	0.5681	pathogenic	-0.031	Destabilizing	0.998	D	0.727	deleterious	None	None	None	None	N
S/E	0.8647	likely_pathogenic	0.8105	pathogenic	-0.145	Destabilizing	0.998	D	0.739	deleterious	None	None	None	None	N
S/F	0.7175	likely_pathogenic	0.6181	pathogenic	-0.928	Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
S/G	0.1888	likely_benign	0.1392	benign	-0.262	Destabilizing	0.997	D	0.53	neutral	N	0.490841988	None	None	N
S/H	0.7122	likely_pathogenic	0.6121	pathogenic	-0.68	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
S/I	0.7229	likely_pathogenic	0.6199	pathogenic	-0.192	Destabilizing	0.999	D	0.765	deleterious	N	0.521511612	None	None	N
S/K	0.9535	likely_pathogenic	0.9182	pathogenic	-0.355	Destabilizing	0.998	D	0.721	deleterious	None	None	None	None	N
S/L	0.3959	ambiguous	0.308	benign	-0.192	Destabilizing	0.999	D	0.671	prob.neutral	None	None	None	None	N
S/M	0.6325	likely_pathogenic	0.5427	ambiguous	0.028	Stabilizing	1.0	D	0.721	deleterious	None	None	None	None	N
S/N	0.3313	likely_benign	0.2441	benign	-0.054	Destabilizing	0.997	D	0.73	deleterious	N	0.429236169	None	None	N
S/P	0.4119	ambiguous	0.313	benign	-0.172	Destabilizing	0.999	D	0.735	deleterious	None	None	None	None	N
S/Q	0.8604	likely_pathogenic	0.7924	pathogenic	-0.337	Destabilizing	0.999	D	0.701	prob.delet.	None	None	None	None	N
S/R	0.9392	likely_pathogenic	0.8943	pathogenic	-0.086	Destabilizing	0.999	D	0.727	deleterious	N	0.502232418	None	None	N
S/T	0.1826	likely_benign	0.1459	benign	-0.173	Destabilizing	0.997	D	0.579	neutral	N	0.436292641	None	None	N
S/V	0.6502	likely_pathogenic	0.551	ambiguous	-0.172	Destabilizing	0.999	D	0.754	deleterious	None	None	None	None	N
S/W	0.7438	likely_pathogenic	0.681	pathogenic	-0.98	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
S/Y	0.5477	ambiguous	0.4597	ambiguous	-0.676	Destabilizing	0.999	D	0.8	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.