TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16244	48955;48956;48957	chr2:178614877;178614876;178614875	chr2:179479604;179479603;179479602
N2AB	14603	44032;44033;44034	chr2:178614877;178614876;178614875	chr2:179479604;179479603;179479602
N2A	13676	41251;41252;41253	chr2:178614877;178614876;178614875	chr2:179479604;179479603;179479602
N2B	7179	21760;21761;21762	chr2:178614877;178614876;178614875	chr2:179479604;179479603;179479602
Novex-1	7304	22135;22136;22137	chr2:178614877;178614876;178614875	chr2:179479604;179479603;179479602
Novex-2	7371	22336;22337;22338	chr2:178614877;178614876;178614875	chr2:179479604;179479603;179479602
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-5
• Domain position: 90
• Structural Position: 124
• Q(SASA): 0.2002
• 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
T/I	None	None	0.999	D	0.869	0.352	0.473458370588	gnomAD-4.0.0	1.69463E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.53271E-05	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
T/A	0.4243	ambiguous	0.3764	ambiguous	-0.862	Destabilizing	0.997	D	0.621	neutral	N	0.48655091	None	None	N
T/C	0.8623	likely_pathogenic	0.8789	pathogenic	-0.506	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
T/D	0.9663	likely_pathogenic	0.955	pathogenic	-0.519	Destabilizing	0.999	D	0.859	deleterious	None	None	None	None	N
T/E	0.9644	likely_pathogenic	0.9431	pathogenic	-0.386	Destabilizing	0.999	D	0.856	deleterious	None	None	None	None	N
T/F	0.9518	likely_pathogenic	0.9441	pathogenic	-0.607	Destabilizing	0.999	D	0.888	deleterious	None	None	None	None	N
T/G	0.6367	likely_pathogenic	0.5992	pathogenic	-1.243	Destabilizing	0.999	D	0.84	deleterious	None	None	None	None	N
T/H	0.9589	likely_pathogenic	0.9554	pathogenic	-1.407	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
T/I	0.8795	likely_pathogenic	0.8672	pathogenic	0.108	Stabilizing	0.999	D	0.869	deleterious	D	0.54504032	None	None	N
T/K	0.9606	likely_pathogenic	0.9452	pathogenic	-0.543	Destabilizing	0.999	D	0.858	deleterious	N	0.52144978	None	None	N
T/L	0.5746	likely_pathogenic	0.5358	ambiguous	0.108	Stabilizing	0.998	D	0.739	deleterious	None	None	None	None	N
T/M	0.4652	ambiguous	0.4367	ambiguous	0.103	Stabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
T/N	0.7748	likely_pathogenic	0.7747	pathogenic	-0.912	Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	N
T/P	0.8624	likely_pathogenic	0.7857	pathogenic	-0.182	Destabilizing	0.999	D	0.844	deleterious	N	0.490260171	None	None	N
T/Q	0.9257	likely_pathogenic	0.9075	pathogenic	-0.77	Destabilizing	0.999	D	0.833	deleterious	None	None	None	None	N
T/R	0.9552	likely_pathogenic	0.9382	pathogenic	-0.646	Destabilizing	0.999	D	0.842	deleterious	D	0.641718052	None	None	N
T/S	0.3262	likely_benign	0.3422	ambiguous	-1.194	Destabilizing	0.997	D	0.609	neutral	N	0.453884852	None	None	N
T/V	0.6617	likely_pathogenic	0.6372	pathogenic	-0.182	Destabilizing	0.998	D	0.618	neutral	None	None	None	None	N
T/W	0.9901	likely_pathogenic	0.9861	pathogenic	-0.691	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
T/Y	0.9789	likely_pathogenic	0.9744	pathogenic	-0.356	Destabilizing	1.0	D	0.902	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.