TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21189	63790;63791;63792	chr2:178587744;178587743;178587742	chr2:179452471;179452470;179452469
N2AB	19548	58867;58868;58869	chr2:178587744;178587743;178587742	chr2:179452471;179452470;179452469
N2A	18621	56086;56087;56088	chr2:178587744;178587743;178587742	chr2:179452471;179452470;179452469
N2B	12124	36595;36596;36597	chr2:178587744;178587743;178587742	chr2:179452471;179452470;179452469
Novex-1	12249	36970;36971;36972	chr2:178587744;178587743;178587742	chr2:179452471;179452470;179452469
Novex-2	12316	37171;37172;37173	chr2:178587744;178587743;178587742	chr2:179452471;179452470;179452469
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: Ig-123
• Domain position: 13
• Structural Position: 24
• Q(SASA): 0.238
• 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/V	None	None	0.999	D	0.834	0.823	0.879814937172	gnomAD-4.0.0	1.36963E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.8E-06	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	0.5812	likely_pathogenic	0.5686	pathogenic	-0.294	Destabilizing	0.991	D	0.693	prob.neutral	D	0.598287855	None	None	I
G/C	0.6756	likely_pathogenic	0.6687	pathogenic	-0.831	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
G/D	0.787	likely_pathogenic	0.7703	pathogenic	-0.773	Destabilizing	0.996	D	0.839	deleterious	None	None	None	None	I
G/E	0.8789	likely_pathogenic	0.8584	pathogenic	-0.952	Destabilizing	0.652	D	0.601	neutral	D	0.608715623	None	None	I
G/F	0.9698	likely_pathogenic	0.968	pathogenic	-1.139	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
G/H	0.8786	likely_pathogenic	0.8732	pathogenic	-0.52	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	I
G/I	0.9654	likely_pathogenic	0.9582	pathogenic	-0.506	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	I
G/K	0.9238	likely_pathogenic	0.9182	pathogenic	-0.742	Destabilizing	0.996	D	0.837	deleterious	None	None	None	None	I
G/L	0.9307	likely_pathogenic	0.9323	pathogenic	-0.506	Destabilizing	0.998	D	0.832	deleterious	None	None	None	None	I
G/M	0.9425	likely_pathogenic	0.943	pathogenic	-0.397	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	I
G/N	0.6643	likely_pathogenic	0.6689	pathogenic	-0.407	Destabilizing	0.998	D	0.841	deleterious	None	None	None	None	I
G/P	0.9948	likely_pathogenic	0.9938	pathogenic	-0.405	Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	I
G/Q	0.8191	likely_pathogenic	0.8081	pathogenic	-0.749	Destabilizing	0.996	D	0.851	deleterious	None	None	None	None	I
G/R	0.8297	likely_pathogenic	0.8039	pathogenic	-0.25	Destabilizing	0.997	D	0.85	deleterious	D	0.619616643	None	None	I
G/S	0.3335	likely_benign	0.3286	benign	-0.505	Destabilizing	0.998	D	0.831	deleterious	None	None	None	None	I
G/T	0.7574	likely_pathogenic	0.7339	pathogenic	-0.624	Destabilizing	0.998	D	0.839	deleterious	None	None	None	None	I
G/V	0.9201	likely_pathogenic	0.9057	pathogenic	-0.405	Destabilizing	0.999	D	0.834	deleterious	D	0.652089334	None	None	I
G/W	0.9568	likely_pathogenic	0.9462	pathogenic	-1.26	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	I
G/Y	0.9408	likely_pathogenic	0.9399	pathogenic	-0.916	Destabilizing	1.0	D	0.865	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.