TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8307	25144;25145;25146	chr2:178718087;178718086;178718085	chr2:179582814;179582813;179582812
N2AB	7990	24193;24194;24195	chr2:178718087;178718086;178718085	chr2:179582814;179582813;179582812
N2A	7063	21412;21413;21414	chr2:178718087;178718086;178718085	chr2:179582814;179582813;179582812
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-68
• Domain position: 44
• Structural Position: 73
• Q(SASA): 0.3233
• 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	rs2077769834	None	None	N	0.106	0.216	0.295974979623	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.6278	likely_pathogenic	0.6965	pathogenic	-0.725	Destabilizing	0.996	D	0.334	neutral	None	None	None	None	N
A/D	0.4231	ambiguous	0.5725	pathogenic	-0.42	Destabilizing	0.7	D	0.414	neutral	N	0.407711678	None	None	N
A/E	0.4279	ambiguous	0.5506	ambiguous	-0.55	Destabilizing	0.812	D	0.383	neutral	None	None	None	None	N
A/F	0.3985	ambiguous	0.4784	ambiguous	-0.811	Destabilizing	0.988	D	0.413	neutral	None	None	None	None	N
A/G	0.1604	likely_benign	0.2219	benign	-0.373	Destabilizing	None	N	0.106	neutral	N	0.344814992	None	None	N
A/H	0.5331	ambiguous	0.6372	pathogenic	-0.372	Destabilizing	0.996	D	0.369	neutral	None	None	None	None	N
A/I	0.3251	likely_benign	0.4098	ambiguous	-0.283	Destabilizing	0.976	D	0.395	neutral	None	None	None	None	N
A/K	0.6528	likely_pathogenic	0.7777	pathogenic	-0.675	Destabilizing	0.92	D	0.381	neutral	None	None	None	None	N
A/L	0.1913	likely_benign	0.245	benign	-0.283	Destabilizing	0.852	D	0.367	neutral	None	None	None	None	N
A/M	0.2667	likely_benign	0.3317	benign	-0.454	Destabilizing	0.996	D	0.318	neutral	None	None	None	None	N
A/N	0.2733	likely_benign	0.3672	ambiguous	-0.345	Destabilizing	0.266	N	0.402	neutral	None	None	None	None	N
A/P	0.5621	ambiguous	0.6959	pathogenic	-0.253	Destabilizing	0.825	D	0.419	neutral	N	0.474168743	None	None	N
A/Q	0.4476	ambiguous	0.5467	ambiguous	-0.574	Destabilizing	0.976	D	0.369	neutral	None	None	None	None	N
A/R	0.6083	likely_pathogenic	0.7234	pathogenic	-0.245	Destabilizing	0.976	D	0.389	neutral	None	None	None	None	N
A/S	0.0805	likely_benign	0.0907	benign	-0.559	Destabilizing	0.001	N	0.119	neutral	N	0.341369255	None	None	N
A/T	0.0863	likely_benign	0.1023	benign	-0.603	Destabilizing	0.009	N	0.126	neutral	N	0.39636132	None	None	N
A/V	0.1601	likely_benign	0.205	benign	-0.253	Destabilizing	0.62	D	0.341	neutral	N	0.468146848	None	None	N
A/W	0.8309	likely_pathogenic	0.8914	pathogenic	-0.982	Destabilizing	0.999	D	0.445	neutral	None	None	None	None	N
A/Y	0.5767	likely_pathogenic	0.6659	pathogenic	-0.63	Destabilizing	0.996	D	0.393	neutral	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.