TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9382	28369;28370;28371	chr2:178711092;178711091;178711090	chr2:179575819;179575818;179575817
N2AB	9065	27418;27419;27420	chr2:178711092;178711091;178711090	chr2:179575819;179575818;179575817
N2A	8138	24637;24638;24639	chr2:178711092;178711091;178711090	chr2:179575819;179575818;179575817
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-79
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.1665
• 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
A/G	None	None	0.989	None	0.529	0.471	0.503248607038	gnomAD-4.0.0	3.23474E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.94724E-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
A/C	0.5912	likely_pathogenic	0.6412	pathogenic	-0.809	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
A/D	0.3345	likely_benign	0.4517	ambiguous	0.14	Stabilizing	0.997	D	0.779	deleterious	None	None	None	None	N
A/E	0.3388	likely_benign	0.4497	ambiguous	0.04	Stabilizing	0.998	D	0.729	prob.delet.	None	None	None	None	N
A/F	0.4335	ambiguous	0.4957	ambiguous	-0.88	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
A/G	0.2449	likely_benign	0.2598	benign	-0.631	Destabilizing	0.989	D	0.529	neutral	None	None	None	None	N
A/H	0.5562	ambiguous	0.6281	pathogenic	-0.649	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
A/I	0.3119	likely_benign	0.3581	ambiguous	-0.313	Destabilizing	0.998	D	0.798	deleterious	None	None	None	None	N
A/K	0.4638	ambiguous	0.5932	pathogenic	-0.506	Destabilizing	0.998	D	0.729	prob.delet.	None	None	None	None	N
A/L	0.3024	likely_benign	0.3367	benign	-0.313	Destabilizing	0.992	D	0.661	neutral	None	None	None	None	N
A/M	0.3404	ambiguous	0.3853	ambiguous	-0.392	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
A/N	0.3501	ambiguous	0.4084	ambiguous	-0.216	Destabilizing	0.998	D	0.794	deleterious	None	None	None	None	N
A/P	0.9548	likely_pathogenic	0.9762	pathogenic	-0.336	Destabilizing	0.998	D	0.804	deleterious	None	None	None	None	N
A/Q	0.3866	ambiguous	0.4748	ambiguous	-0.403	Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
A/R	0.3898	ambiguous	0.4983	ambiguous	-0.224	Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	N
A/S	0.1043	likely_benign	0.1054	benign	-0.616	Destabilizing	0.775	D	0.373	neutral	None	None	None	None	N
A/T	0.0933	likely_benign	0.1006	benign	-0.613	Destabilizing	0.733	D	0.367	neutral	None	None	None	None	N
A/V	0.138	likely_benign	0.1504	benign	-0.336	Destabilizing	0.989	D	0.607	neutral	None	None	None	None	N
A/W	0.8967	likely_pathogenic	0.9332	pathogenic	-1.041	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
A/Y	0.6287	likely_pathogenic	0.7086	pathogenic	-0.656	Destabilizing	1.0	D	0.821	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.