TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18665	56218;56219;56220	chr2:178600911;178600910;178600909	chr2:179465638;179465637;179465636
N2AB	17024	51295;51296;51297	chr2:178600911;178600910;178600909	chr2:179465638;179465637;179465636
N2A	16097	48514;48515;48516	chr2:178600911;178600910;178600909	chr2:179465638;179465637;179465636
N2B	9600	29023;29024;29025	chr2:178600911;178600910;178600909	chr2:179465638;179465637;179465636
Novex-1	9725	29398;29399;29400	chr2:178600911;178600910;178600909	chr2:179465638;179465637;179465636
Novex-2	9792	29599;29600;29601	chr2:178600911;178600910;178600909	chr2:179465638;179465637;179465636
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-23
• Domain position: 87
• Structural Position: 114
• Q(SASA): 0.4532
• Predicted PPI site: I

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
A/V	None	None	1.0	N	0.704	0.397	0.427596317008	gnomAD-4.0.0	6.84532E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99831E-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
A/C	0.6509	likely_pathogenic	0.6284	pathogenic	-0.82	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
A/D	0.9401	likely_pathogenic	0.9264	pathogenic	-0.495	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	I
A/E	0.8521	likely_pathogenic	0.8135	pathogenic	-0.652	Destabilizing	1.0	D	0.797	deleterious	N	0.519865668	None	None	I
A/F	0.6833	likely_pathogenic	0.6163	pathogenic	-0.883	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	I
A/G	0.3669	ambiguous	0.4086	ambiguous	-0.212	Destabilizing	1.0	D	0.607	neutral	N	0.476457666	None	None	I
A/H	0.8708	likely_pathogenic	0.8415	pathogenic	-0.165	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
A/I	0.5568	ambiguous	0.443	ambiguous	-0.377	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
A/K	0.9134	likely_pathogenic	0.9123	pathogenic	-0.511	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	I
A/L	0.5574	ambiguous	0.51	ambiguous	-0.377	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
A/M	0.5572	ambiguous	0.4821	ambiguous	-0.493	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
A/N	0.8038	likely_pathogenic	0.7464	pathogenic	-0.229	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	I
A/P	0.9434	likely_pathogenic	0.955	pathogenic	-0.292	Destabilizing	1.0	D	0.811	deleterious	N	0.513733041	None	None	I
A/Q	0.7685	likely_pathogenic	0.7434	pathogenic	-0.512	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
A/R	0.8182	likely_pathogenic	0.8311	pathogenic	-0.045	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
A/S	0.2135	likely_benign	0.1892	benign	-0.417	Destabilizing	1.0	D	0.607	neutral	N	0.512729052	None	None	I
A/T	0.3298	likely_benign	0.3054	benign	-0.5	Destabilizing	1.0	D	0.768	deleterious	N	0.473383474	None	None	I
A/V	0.2423	likely_benign	0.1794	benign	-0.292	Destabilizing	1.0	D	0.704	prob.neutral	N	0.44202096	None	None	I
A/W	0.9525	likely_pathogenic	0.9516	pathogenic	-0.98	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
A/Y	0.8625	likely_pathogenic	0.8393	pathogenic	-0.654	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	I

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.