TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8552	25879;25880;25881	chr2:178715760;178715759;178715758	chr2:179580487;179580486;179580485
N2AB	8235	24928;24929;24930	chr2:178715760;178715759;178715758	chr2:179580487;179580486;179580485
N2A	7308	22147;22148;22149	chr2:178715760;178715759;178715758	chr2:179580487;179580486;179580485
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-71
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.5483
• 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/T	rs940884256	-0.629	0.003	N	0.135	0.213	0.379020345274	gnomAD-2.1.1	5E-06	None	None	None	None	N	None	8.43E-05	0	None	0	0	None	0	None	0	0	0
I/T	rs940884256	-0.629	0.003	N	0.135	0.213	0.379020345274	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
I/T	rs940884256	-0.629	0.003	N	0.135	0.213	0.379020345274	gnomAD-4.0.0	5.05384E-06	None	None	None	None	N	None	9.42177E-05	0	None	0	0	None	0	0	0	0	1.63068E-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
I/A	0.5002	ambiguous	0.5299	ambiguous	-1.197	Destabilizing	0.359	N	0.343	neutral	None	None	None	None	N
I/C	0.8092	likely_pathogenic	0.824	pathogenic	-0.81	Destabilizing	0.996	D	0.355	neutral	None	None	None	None	N
I/D	0.8871	likely_pathogenic	0.8962	pathogenic	-0.544	Destabilizing	0.905	D	0.389	neutral	None	None	None	None	N
I/E	0.7682	likely_pathogenic	0.7778	pathogenic	-0.567	Destabilizing	0.875	D	0.398	neutral	None	None	None	None	N
I/F	0.2025	likely_benign	0.2119	benign	-0.762	Destabilizing	0.853	D	0.355	neutral	N	0.47049146	None	None	N
I/G	0.7542	likely_pathogenic	0.7675	pathogenic	-1.465	Destabilizing	0.73	D	0.381	neutral	None	None	None	None	N
I/H	0.5848	likely_pathogenic	0.6092	pathogenic	-0.496	Destabilizing	0.989	D	0.36	neutral	None	None	None	None	N
I/K	0.5841	likely_pathogenic	0.5989	pathogenic	-0.828	Destabilizing	0.219	N	0.39	neutral	None	None	None	None	N
I/L	0.115	likely_benign	0.1162	benign	-0.561	Destabilizing	0.005	N	0.182	neutral	N	0.46278773	None	None	N
I/M	0.1315	likely_benign	0.135	benign	-0.538	Destabilizing	0.635	D	0.376	neutral	N	0.453401163	None	None	N
I/N	0.4178	ambiguous	0.4347	ambiguous	-0.682	Destabilizing	0.878	D	0.396	neutral	N	0.457769256	None	None	N
I/P	0.889	likely_pathogenic	0.8859	pathogenic	-0.74	Destabilizing	0.951	D	0.402	neutral	None	None	None	None	N
I/Q	0.511	ambiguous	0.522	ambiguous	-0.862	Destabilizing	0.889	D	0.38	neutral	None	None	None	None	N
I/R	0.479	ambiguous	0.4954	ambiguous	-0.193	Destabilizing	0.791	D	0.396	neutral	None	None	None	None	N
I/S	0.3704	ambiguous	0.3904	ambiguous	-1.253	Destabilizing	0.506	D	0.373	neutral	N	0.486627381	None	None	N
I/T	0.2919	likely_benign	0.3186	benign	-1.163	Destabilizing	0.003	N	0.135	neutral	N	0.413188415	None	None	N
I/V	0.0896	likely_benign	0.0929	benign	-0.74	Destabilizing	None	N	0.108	neutral	N	0.391503634	None	None	N
I/W	0.7829	likely_pathogenic	0.7924	pathogenic	-0.787	Destabilizing	0.997	D	0.422	neutral	None	None	None	None	N
I/Y	0.5732	likely_pathogenic	0.5888	pathogenic	-0.579	Destabilizing	0.732	D	0.381	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.