TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22909	68950;68951;68952	chr2:178577701;178577700;178577699	chr2:179442428;179442427;179442426
N2AB	21268	64027;64028;64029	chr2:178577701;178577700;178577699	chr2:179442428;179442427;179442426
N2A	20341	61246;61247;61248	chr2:178577701;178577700;178577699	chr2:179442428;179442427;179442426
N2B	13844	41755;41756;41757	chr2:178577701;178577700;178577699	chr2:179442428;179442427;179442426
Novex-1	13969	42130;42131;42132	chr2:178577701;178577700;178577699	chr2:179442428;179442427;179442426
Novex-2	14036	42331;42332;42333	chr2:178577701;178577700;178577699	chr2:179442428;179442427;179442426
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-54
• Domain position: 69
• Structural Position: 100
• Q(SASA): 0.4587
• 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/S	rs1229308935	None	0.999	N	0.774	0.516	0.323342291347	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	1.93798E-04	None	0	0	0	0	0
G/S	rs1229308935	None	0.999	N	0.774	0.516	0.323342291347	gnomAD-4.0.0	6.57696E-06	None	None	None	None	I	None	0	0	None	0	1.93798E-04	None	0	0	0	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	0.2978	likely_benign	0.3246	benign	-0.446	Destabilizing	0.995	D	0.647	neutral	N	0.492509049	None	None	I
G/C	0.441	ambiguous	0.4983	ambiguous	-0.94	Destabilizing	1.0	D	0.861	deleterious	D	0.552964334	None	None	I
G/D	0.2082	likely_benign	0.2476	benign	-0.827	Destabilizing	0.999	D	0.78	deleterious	N	0.490839201	None	None	I
G/E	0.3848	ambiguous	0.438	ambiguous	-0.975	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	I
G/F	0.7714	likely_pathogenic	0.8104	pathogenic	-1.027	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	I
G/H	0.6056	likely_pathogenic	0.65	pathogenic	-0.719	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
G/I	0.7495	likely_pathogenic	0.8005	pathogenic	-0.477	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	I
G/K	0.7147	likely_pathogenic	0.7621	pathogenic	-1.098	Destabilizing	0.998	D	0.841	deleterious	None	None	None	None	I
G/L	0.7176	likely_pathogenic	0.7542	pathogenic	-0.477	Destabilizing	0.999	D	0.862	deleterious	None	None	None	None	I
G/M	0.7154	likely_pathogenic	0.7498	pathogenic	-0.49	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	I
G/N	0.2296	likely_benign	0.2536	benign	-0.712	Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	I
G/P	0.979	likely_pathogenic	0.9845	pathogenic	-0.431	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	I
G/Q	0.5899	likely_pathogenic	0.6286	pathogenic	-1.003	Destabilizing	0.999	D	0.879	deleterious	None	None	None	None	I
G/R	0.65	likely_pathogenic	0.6936	pathogenic	-0.597	Destabilizing	0.777	D	0.648	neutral	D	0.52519884	None	None	I
G/S	0.1652	likely_benign	0.1769	benign	-0.865	Destabilizing	0.999	D	0.774	deleterious	N	0.493963853	None	None	I
G/T	0.3534	ambiguous	0.3958	ambiguous	-0.946	Destabilizing	0.999	D	0.858	deleterious	None	None	None	None	I
G/V	0.6169	likely_pathogenic	0.6767	pathogenic	-0.431	Destabilizing	0.999	D	0.869	deleterious	D	0.541101049	None	None	I
G/W	0.6456	likely_pathogenic	0.6787	pathogenic	-1.203	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	I
G/Y	0.5593	ambiguous	0.6215	pathogenic	-0.868	Destabilizing	1.0	D	0.867	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.