TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28685	86278;86279;86280	chr2:178560079;178560078;178560077	chr2:179424806;179424805;179424804
N2AB	27044	81355;81356;81357	chr2:178560079;178560078;178560077	chr2:179424806;179424805;179424804
N2A	26117	78574;78575;78576	chr2:178560079;178560078;178560077	chr2:179424806;179424805;179424804
N2B	19620	59083;59084;59085	chr2:178560079;178560078;178560077	chr2:179424806;179424805;179424804
Novex-1	19745	59458;59459;59460	chr2:178560079;178560078;178560077	chr2:179424806;179424805;179424804
Novex-2	19812	59659;59660;59661	chr2:178560079;178560078;178560077	chr2:179424806;179424805;179424804
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: Fn3-97
• Domain position: 35
• Structural Position: 37
• Q(SASA): 0.1134
• 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
G/R	rs1267717857	None	0.997	N	0.908	0.45	0.691819975625	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	0	4.78927E-04
G/R	rs1267717857	None	0.997	N	0.908	0.45	0.691819975625	gnomAD-4.0.0	6.57739E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	4.78927E-04

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	0.3083	likely_benign	0.3428	ambiguous	-0.585	Destabilizing	0.117	N	0.425	neutral	N	0.490379001	None	None	N
G/C	0.5722	likely_pathogenic	0.5766	pathogenic	-1.037	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
G/D	0.8724	likely_pathogenic	0.8514	pathogenic	-0.642	Destabilizing	0.998	D	0.852	deleterious	None	None	None	None	N
G/E	0.902	likely_pathogenic	0.8926	pathogenic	-0.657	Destabilizing	0.993	D	0.895	deleterious	N	0.481478231	None	None	N
G/F	0.9505	likely_pathogenic	0.9552	pathogenic	-0.853	Destabilizing	0.999	D	0.903	deleterious	None	None	None	None	N
G/H	0.8574	likely_pathogenic	0.8475	pathogenic	-1.108	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
G/I	0.9507	likely_pathogenic	0.9554	pathogenic	-0.143	Destabilizing	0.995	D	0.912	deleterious	None	None	None	None	N
G/K	0.9482	likely_pathogenic	0.9466	pathogenic	-0.729	Destabilizing	0.995	D	0.898	deleterious	None	None	None	None	N
G/L	0.9357	likely_pathogenic	0.9396	pathogenic	-0.143	Destabilizing	0.995	D	0.885	deleterious	None	None	None	None	N
G/M	0.931	likely_pathogenic	0.9351	pathogenic	-0.398	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
G/N	0.8091	likely_pathogenic	0.7766	pathogenic	-0.544	Destabilizing	0.998	D	0.703	prob.neutral	None	None	None	None	N
G/P	0.9992	likely_pathogenic	0.9993	pathogenic	-0.25	Destabilizing	0.998	D	0.905	deleterious	None	None	None	None	N
G/Q	0.864	likely_pathogenic	0.8588	pathogenic	-0.66	Destabilizing	0.999	D	0.897	deleterious	None	None	None	None	N
G/R	0.8624	likely_pathogenic	0.8633	pathogenic	-0.649	Destabilizing	0.997	D	0.908	deleterious	N	0.491998389	None	None	N
G/S	0.2203	likely_benign	0.2119	benign	-0.937	Destabilizing	0.966	D	0.564	neutral	None	None	None	None	N
G/T	0.7036	likely_pathogenic	0.7119	pathogenic	-0.856	Destabilizing	0.995	D	0.874	deleterious	None	None	None	None	N
G/V	0.8997	likely_pathogenic	0.9085	pathogenic	-0.25	Destabilizing	0.987	D	0.871	deleterious	D	0.529563252	None	None	N
G/W	0.91	likely_pathogenic	0.9213	pathogenic	-1.189	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
G/Y	0.892	likely_pathogenic	0.892	pathogenic	-0.72	Destabilizing	1.0	D	0.898	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.