TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5405	16438;16439;16440	chr2:178732963;178732962;178732961	chr2:179597690;179597689;179597688
N2AB	5088	15487;15488;15489	chr2:178732963;178732962;178732961	chr2:179597690;179597689;179597688
N2A	4161	12706;12707;12708	chr2:178732963;178732962;178732961	chr2:179597690;179597689;179597688
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: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-37
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.3257
• Predicted PPI site: I

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	None	None	0.171	D	0.444	0.249	0.449572021084	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
I/T	rs1165296614	-1.564	0.001	N	0.267	0.405	0.656662538205	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	0	0	None	0	6.49351E-04	None	0	None	0	0	0
I/T	rs1165296614	-1.564	0.001	N	0.267	0.405	0.656662538205	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	1.93874E-04	None	0	0	0	0	0
I/T	rs1165296614	-1.564	0.001	N	0.267	0.405	0.656662538205	gnomAD-4.0.0	2.56293E-06	None	None	None	None	I	None	0	0	None	0	4.86287E-05	None	0	0	0	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	0.237	likely_benign	0.2489	benign	-1.715	Destabilizing	None	N	0.189	neutral	None	None	None	None	I
I/C	0.687	likely_pathogenic	0.7154	pathogenic	-1.115	Destabilizing	0.356	N	0.505	neutral	None	None	None	None	I
I/D	0.7231	likely_pathogenic	0.7541	pathogenic	-0.985	Destabilizing	0.072	N	0.591	neutral	None	None	None	None	I
I/E	0.5218	ambiguous	0.543	ambiguous	-0.9	Destabilizing	0.072	N	0.539	neutral	None	None	None	None	I
I/F	0.137	likely_benign	0.1519	benign	-1.023	Destabilizing	0.12	N	0.46	neutral	None	None	None	None	I
I/G	0.5921	likely_pathogenic	0.6291	pathogenic	-2.121	Highly Destabilizing	0.038	N	0.499	neutral	None	None	None	None	I
I/H	0.5104	ambiguous	0.5455	ambiguous	-1.348	Destabilizing	0.864	D	0.545	neutral	None	None	None	None	I
I/K	0.3972	ambiguous	0.3998	ambiguous	-1.152	Destabilizing	0.055	N	0.539	neutral	N	0.504511962	None	None	I
I/L	0.1005	likely_benign	0.101	benign	-0.639	Destabilizing	None	N	0.101	neutral	N	0.518532809	None	None	I
I/M	0.0716	likely_benign	0.0717	benign	-0.593	Destabilizing	0.171	N	0.444	neutral	D	0.526941648	None	None	I
I/N	0.3303	likely_benign	0.3524	ambiguous	-1.13	Destabilizing	0.356	N	0.621	neutral	None	None	None	None	I
I/P	0.5345	ambiguous	0.589	pathogenic	-0.968	Destabilizing	None	N	0.379	neutral	None	None	None	None	I
I/Q	0.4201	ambiguous	0.4374	ambiguous	-1.157	Destabilizing	0.356	N	0.585	neutral	None	None	None	None	I
I/R	0.3125	likely_benign	0.3234	benign	-0.743	Destabilizing	0.171	N	0.621	neutral	D	0.52418638	None	None	I
I/S	0.2736	likely_benign	0.2946	benign	-1.839	Destabilizing	0.016	N	0.394	neutral	None	None	None	None	I
I/T	0.1368	likely_benign	0.1446	benign	-1.616	Destabilizing	0.001	N	0.267	neutral	N	0.498352325	None	None	I
I/V	0.0789	likely_benign	0.0823	benign	-0.968	Destabilizing	None	N	0.139	neutral	N	0.513257488	None	None	I
I/W	0.6859	likely_pathogenic	0.72	pathogenic	-1.175	Destabilizing	0.864	D	0.581	neutral	None	None	None	None	I
I/Y	0.4459	ambiguous	0.4857	ambiguous	-0.904	Destabilizing	0.356	N	0.533	neutral	None	None	None	None	I

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.