TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33420	100483;100484;100485	chr2:178536489;178536488;178536487	chr2:179401216;179401215;179401214
N2AB	31779	95560;95561;95562	chr2:178536489;178536488;178536487	chr2:179401216;179401215;179401214
N2A	30852	92779;92780;92781	chr2:178536489;178536488;178536487	chr2:179401216;179401215;179401214
N2B	24355	73288;73289;73290	chr2:178536489;178536488;178536487	chr2:179401216;179401215;179401214
Novex-1	24480	73663;73664;73665	chr2:178536489;178536488;178536487	chr2:179401216;179401215;179401214
Novex-2	24547	73864;73865;73866	chr2:178536489;178536488;178536487	chr2:179401216;179401215;179401214
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-131
• Domain position: 29
• Structural Position: 31
• Q(SASA): 0.4575
• 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
G/E	None	None	1.0	D	0.865	0.668	0.520161069619	gnomAD-4.0.0	7.03873E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.16113E-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
G/A	0.8656	likely_pathogenic	0.8263	pathogenic	-0.182	Destabilizing	1.0	D	0.73	prob.delet.	N	0.507893236	None	None	I
G/C	0.9537	likely_pathogenic	0.9328	pathogenic	-0.772	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
G/D	0.9804	likely_pathogenic	0.9746	pathogenic	-0.524	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
G/E	0.9873	likely_pathogenic	0.9817	pathogenic	-0.699	Destabilizing	1.0	D	0.865	deleterious	D	0.536846818	None	None	I
G/F	0.9946	likely_pathogenic	0.9923	pathogenic	-1.051	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
G/H	0.9922	likely_pathogenic	0.9884	pathogenic	-0.411	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	I
G/I	0.9931	likely_pathogenic	0.9902	pathogenic	-0.414	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
G/K	0.9895	likely_pathogenic	0.9865	pathogenic	-0.537	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	I
G/L	0.993	likely_pathogenic	0.9888	pathogenic	-0.414	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	I
G/M	0.9967	likely_pathogenic	0.994	pathogenic	-0.349	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
G/N	0.9785	likely_pathogenic	0.9665	pathogenic	-0.224	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	I
G/P	0.9988	likely_pathogenic	0.9986	pathogenic	-0.307	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	I
G/Q	0.9874	likely_pathogenic	0.9812	pathogenic	-0.545	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
G/R	0.9683	likely_pathogenic	0.9577	pathogenic	-0.111	Destabilizing	1.0	D	0.857	deleterious	N	0.507386257	None	None	I
G/S	0.8042	likely_pathogenic	0.7431	pathogenic	-0.344	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
G/T	0.9767	likely_pathogenic	0.9667	pathogenic	-0.456	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	I
G/V	0.9876	likely_pathogenic	0.9811	pathogenic	-0.307	Destabilizing	1.0	D	0.841	deleterious	N	0.5202635	None	None	I
G/W	0.9876	likely_pathogenic	0.9832	pathogenic	-1.176	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
G/Y	0.9924	likely_pathogenic	0.9885	pathogenic	-0.813	Destabilizing	1.0	D	0.813	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.