TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23364	70315;70316;70317	chr2:178576042;178576041;178576040	chr2:179440769;179440768;179440767
N2AB	21723	65392;65393;65394	chr2:178576042;178576041;178576040	chr2:179440769;179440768;179440767
N2A	20796	62611;62612;62613	chr2:178576042;178576041;178576040	chr2:179440769;179440768;179440767
N2B	14299	43120;43121;43122	chr2:178576042;178576041;178576040	chr2:179440769;179440768;179440767
Novex-1	14424	43495;43496;43497	chr2:178576042;178576041;178576040	chr2:179440769;179440768;179440767
Novex-2	14491	43696;43697;43698	chr2:178576042;178576041;178576040	chr2:179440769;179440768;179440767
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-129
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.2164
• 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/L	rs1709965793	None	0.061	N	0.292	0.132	0.330331372229	gnomAD-4.0.0	2.05294E-06	None	None	None	None	N	None	0	0	None	0	5.04134E-05	None	0	0	8.99578E-07	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
I/A	0.9707	likely_pathogenic	0.9794	pathogenic	-2.396	Highly Destabilizing	0.985	D	0.704	prob.neutral	None	None	None	None	N
I/C	0.9637	likely_pathogenic	0.9719	pathogenic	-1.757	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
I/D	0.9991	likely_pathogenic	0.9994	pathogenic	-2.966	Highly Destabilizing	0.999	D	0.859	deleterious	None	None	None	None	N
I/E	0.9983	likely_pathogenic	0.9988	pathogenic	-2.716	Highly Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
I/F	0.7056	likely_pathogenic	0.7752	pathogenic	-1.601	Destabilizing	0.996	D	0.731	prob.delet.	None	None	None	None	N
I/G	0.9957	likely_pathogenic	0.997	pathogenic	-2.863	Highly Destabilizing	0.998	D	0.854	deleterious	None	None	None	None	N
I/H	0.9961	likely_pathogenic	0.9972	pathogenic	-2.269	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
I/K	0.9956	likely_pathogenic	0.9967	pathogenic	-2.083	Highly Destabilizing	0.997	D	0.853	deleterious	N	0.506407612	None	None	N
I/L	0.1511	likely_benign	0.1674	benign	-1.012	Destabilizing	0.061	N	0.292	neutral	N	0.383474089	None	None	N
I/M	0.3195	likely_benign	0.3734	ambiguous	-1.009	Destabilizing	0.817	D	0.479	neutral	N	0.506160944	None	None	N
I/N	0.9875	likely_pathogenic	0.9914	pathogenic	-2.648	Highly Destabilizing	0.999	D	0.856	deleterious	None	None	None	None	N
I/P	0.9975	likely_pathogenic	0.9981	pathogenic	-1.463	Destabilizing	0.999	D	0.856	deleterious	None	None	None	None	N
I/Q	0.9957	likely_pathogenic	0.9967	pathogenic	-2.413	Highly Destabilizing	0.998	D	0.853	deleterious	None	None	None	None	N
I/R	0.9935	likely_pathogenic	0.9951	pathogenic	-2.005	Highly Destabilizing	0.997	D	0.858	deleterious	N	0.506407612	None	None	N
I/S	0.9871	likely_pathogenic	0.9915	pathogenic	-3.17	Highly Destabilizing	0.998	D	0.824	deleterious	None	None	None	None	N
I/T	0.9869	likely_pathogenic	0.9913	pathogenic	-2.773	Highly Destabilizing	0.99	D	0.773	deleterious	N	0.506154123	None	None	N
I/V	0.2215	likely_benign	0.2422	benign	-1.463	Destabilizing	0.817	D	0.439	neutral	N	0.495117231	None	None	N
I/W	0.9943	likely_pathogenic	0.9959	pathogenic	-1.846	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
I/Y	0.9646	likely_pathogenic	0.9727	pathogenic	-1.616	Destabilizing	0.999	D	0.769	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.