TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3270	10033;10034;10035	chr2:178764707;178764706;178764705	chr2:179629434;179629433;179629432
N2AB	3270	10033;10034;10035	chr2:178764707;178764706;178764705	chr2:179629434;179629433;179629432
N2A	3270	10033;10034;10035	chr2:178764707;178764706;178764705	chr2:179629434;179629433;179629432
N2B	3224	9895;9896;9897	chr2:178764707;178764706;178764705	chr2:179629434;179629433;179629432
Novex-1	3224	9895;9896;9897	chr2:178764707;178764706;178764705	chr2:179629434;179629433;179629432
Novex-2	3224	9895;9896;9897	chr2:178764707;178764706;178764705	chr2:179629434;179629433;179629432
Novex-3	3270	10033;10034;10035	chr2:178764707;178764706;178764705	chr2:179629434;179629433;179629432

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-23
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.1545
• 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
I/M	rs1447409995	-0.808	0.901	D	0.697	0.472	0.651879210792	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.83E-06	0
I/T	None	None	0.722	D	0.716	0.603	0.74021432234	gnomAD-4.0.0	1.36815E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99302E-07	1.15934E-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
I/A	0.8448	likely_pathogenic	0.943	pathogenic	-2.237	Highly Destabilizing	0.415	N	0.71	prob.delet.	None	None	None	None	N
I/C	0.9088	likely_pathogenic	0.9703	pathogenic	-1.301	Destabilizing	0.996	D	0.751	deleterious	None	None	None	None	N
I/D	0.9902	likely_pathogenic	0.9984	pathogenic	-1.903	Destabilizing	0.987	D	0.846	deleterious	None	None	None	None	N
I/E	0.9782	likely_pathogenic	0.9958	pathogenic	-1.753	Destabilizing	0.961	D	0.82	deleterious	None	None	None	None	N
I/F	0.4257	ambiguous	0.6598	pathogenic	-1.412	Destabilizing	0.901	D	0.701	prob.neutral	D	0.593914605	None	None	N
I/G	0.9691	likely_pathogenic	0.9923	pathogenic	-2.685	Highly Destabilizing	0.961	D	0.796	deleterious	None	None	None	None	N
I/H	0.9615	likely_pathogenic	0.9933	pathogenic	-1.83	Destabilizing	0.996	D	0.829	deleterious	None	None	None	None	N
I/K	0.9471	likely_pathogenic	0.9909	pathogenic	-1.501	Destabilizing	0.961	D	0.825	deleterious	None	None	None	None	N
I/L	0.2672	likely_benign	0.4188	ambiguous	-0.983	Destabilizing	0.19	N	0.443	neutral	N	0.5190928	None	None	N
I/M	0.2867	likely_benign	0.4731	ambiguous	-0.806	Destabilizing	0.901	D	0.697	prob.neutral	D	0.664873953	None	None	N
I/N	0.8893	likely_pathogenic	0.9744	pathogenic	-1.556	Destabilizing	0.983	D	0.846	deleterious	D	0.741566061	None	None	N
I/P	0.9321	likely_pathogenic	0.9769	pathogenic	-1.379	Destabilizing	0.987	D	0.848	deleterious	None	None	None	None	N
I/Q	0.9603	likely_pathogenic	0.9925	pathogenic	-1.547	Destabilizing	0.987	D	0.841	deleterious	None	None	None	None	N
I/R	0.9241	likely_pathogenic	0.9869	pathogenic	-1.111	Destabilizing	0.961	D	0.845	deleterious	None	None	None	None	N
I/S	0.8946	likely_pathogenic	0.9707	pathogenic	-2.248	Highly Destabilizing	0.901	D	0.804	deleterious	D	0.68082589	None	None	N
I/T	0.7874	likely_pathogenic	0.9316	pathogenic	-1.956	Destabilizing	0.722	D	0.716	prob.delet.	D	0.625607772	None	None	N
I/V	0.0841	likely_benign	0.1198	benign	-1.379	Destabilizing	0.001	N	0.257	neutral	N	0.435856265	None	None	N
I/W	0.9695	likely_pathogenic	0.9929	pathogenic	-1.575	Destabilizing	0.996	D	0.83	deleterious	None	None	None	None	N
I/Y	0.875	likely_pathogenic	0.9631	pathogenic	-1.338	Destabilizing	0.961	D	0.764	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.