TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9766	29521;29522;29523	chr2:178706578;178706577;178706576	chr2:179571305;179571304;179571303
N2AB	9449	28570;28571;28572	chr2:178706578;178706577;178706576	chr2:179571305;179571304;179571303
N2A	8522	25789;25790;25791	chr2:178706578;178706577;178706576	chr2:179571305;179571304;179571303
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: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-83
• Domain position: 69
• Structural Position: 151
• Q(SASA): 0.3046
• 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
S/Y	rs879033462	None	0.999	None	0.824	0.526	None	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
S/A	0.1515	likely_benign	0.1535	benign	-0.853	Destabilizing	0.543	D	0.234	neutral	None	None	None	None	N
S/C	0.4307	ambiguous	0.3597	ambiguous	-0.681	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
S/D	0.9726	likely_pathogenic	0.9187	pathogenic	-0.642	Destabilizing	0.996	D	0.537	neutral	None	None	None	None	N
S/E	0.9474	likely_pathogenic	0.922	pathogenic	-0.643	Destabilizing	0.996	D	0.497	neutral	None	None	None	None	N
S/F	0.8914	likely_pathogenic	0.7666	pathogenic	-1.17	Destabilizing	0.999	D	0.83	deleterious	None	None	None	None	N
S/G	0.3074	likely_benign	0.2285	benign	-1.081	Destabilizing	0.992	D	0.467	neutral	None	None	None	None	N
S/H	0.9315	likely_pathogenic	0.8633	pathogenic	-1.586	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
S/I	0.8287	likely_pathogenic	0.7327	pathogenic	-0.352	Destabilizing	0.999	D	0.798	deleterious	None	None	None	None	N
S/K	0.9804	likely_pathogenic	0.9647	pathogenic	-0.758	Destabilizing	0.996	D	0.495	neutral	None	None	None	None	N
S/L	0.5833	likely_pathogenic	0.4063	ambiguous	-0.352	Destabilizing	0.992	D	0.614	neutral	None	None	None	None	N
S/M	0.6893	likely_pathogenic	0.6209	pathogenic	0.054	Stabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
S/N	0.7272	likely_pathogenic	0.5757	pathogenic	-0.814	Destabilizing	1.0	D	0.579	neutral	None	None	None	None	N
S/P	0.9943	likely_pathogenic	0.9777	pathogenic	-0.488	Destabilizing	0.998	D	0.767	deleterious	None	None	None	None	N
S/Q	0.9098	likely_pathogenic	0.8942	pathogenic	-1.026	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
S/R	0.9579	likely_pathogenic	0.9214	pathogenic	-0.611	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
S/T	0.2762	likely_benign	0.1988	benign	-0.819	Destabilizing	0.989	D	0.449	neutral	None	None	None	None	N
S/V	0.8026	likely_pathogenic	0.7019	pathogenic	-0.488	Destabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	N
S/W	0.9529	likely_pathogenic	0.8785	pathogenic	-1.134	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
S/Y	0.8641	likely_pathogenic	0.7113	pathogenic	-0.857	Destabilizing	0.999	D	0.824	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.