TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33638	101137;101138;101139	chr2:178535703;178535702;178535701	chr2:179400430;179400429;179400428
N2AB	31997	96214;96215;96216	chr2:178535703;178535702;178535701	chr2:179400430;179400429;179400428
N2A	31070	93433;93434;93435	chr2:178535703;178535702;178535701	chr2:179400430;179400429;179400428
N2B	24573	73942;73943;73944	chr2:178535703;178535702;178535701	chr2:179400430;179400429;179400428
Novex-1	24698	74317;74318;74319	chr2:178535703;178535702;178535701	chr2:179400430;179400429;179400428
Novex-2	24765	74518;74519;74520	chr2:178535703;178535702;178535701	chr2:179400430;179400429;179400428
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-159
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.3699
• 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
N/S	rs760140582	0.054	0.864	N	0.372	0.166	0.176091768786	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	1.78E-05	0
N/S	rs760140582	0.054	0.864	N	0.372	0.166	0.176091768786	gnomAD-4.0.0	9.548E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.42924E-05	1.43271E-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
N/A	0.4865	ambiguous	0.2701	benign	-0.397	Destabilizing	0.73	D	0.507	neutral	None	None	None	None	N
N/C	0.5984	likely_pathogenic	0.3551	ambiguous	0.373	Stabilizing	1.0	D	0.649	neutral	None	None	None	None	N
N/D	0.4453	ambiguous	0.2291	benign	-0.02	Destabilizing	0.926	D	0.423	neutral	N	0.476280755	None	None	N
N/E	0.8328	likely_pathogenic	0.592	pathogenic	-0.047	Destabilizing	0.982	D	0.465	neutral	None	None	None	None	N
N/F	0.8965	likely_pathogenic	0.7474	pathogenic	-0.713	Destabilizing	0.999	D	0.678	prob.neutral	None	None	None	None	N
N/G	0.4718	ambiguous	0.2929	benign	-0.589	Destabilizing	0.993	D	0.401	neutral	None	None	None	None	N
N/H	0.3519	ambiguous	0.1814	benign	-0.649	Destabilizing	0.999	D	0.561	neutral	N	0.487618567	None	None	N
N/I	0.6585	likely_pathogenic	0.3883	ambiguous	0.027	Stabilizing	0.995	D	0.673	neutral	N	0.484785595	None	None	N
N/K	0.854	likely_pathogenic	0.5692	pathogenic	0.021	Stabilizing	0.994	D	0.476	neutral	N	0.494173082	None	None	N
N/L	0.5805	likely_pathogenic	0.361	ambiguous	0.027	Stabilizing	0.993	D	0.609	neutral	None	None	None	None	N
N/M	0.7204	likely_pathogenic	0.4836	ambiguous	0.43	Stabilizing	1.0	D	0.605	neutral	None	None	None	None	N
N/P	0.7276	likely_pathogenic	0.477	ambiguous	-0.087	Destabilizing	0.992	D	0.628	neutral	None	None	None	None	N
N/Q	0.7196	likely_pathogenic	0.4631	ambiguous	-0.428	Destabilizing	0.998	D	0.54	neutral	None	None	None	None	N
N/R	0.8156	likely_pathogenic	0.5632	ambiguous	0.063	Stabilizing	0.999	D	0.562	neutral	None	None	None	None	N
N/S	0.1107	likely_benign	0.0751	benign	-0.188	Destabilizing	0.864	D	0.372	neutral	N	0.424406353	None	None	N
N/T	0.2562	likely_benign	0.1299	benign	-0.069	Destabilizing	0.207	N	0.275	neutral	N	0.462196737	None	None	N
N/V	0.597	likely_pathogenic	0.352	ambiguous	-0.087	Destabilizing	0.919	D	0.642	neutral	None	None	None	None	N
N/W	0.9594	likely_pathogenic	0.8918	pathogenic	-0.676	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	N
N/Y	0.5673	likely_pathogenic	0.342	ambiguous	-0.424	Destabilizing	1.0	D	0.633	neutral	N	0.506950378	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.