TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16571	49936;49937;49938	chr2:178613010;178613009;178613008	chr2:179477737;179477736;179477735
N2AB	14930	45013;45014;45015	chr2:178613010;178613009;178613008	chr2:179477737;179477736;179477735
N2A	14003	42232;42233;42234	chr2:178613010;178613009;178613008	chr2:179477737;179477736;179477735
N2B	7506	22741;22742;22743	chr2:178613010;178613009;178613008	chr2:179477737;179477736;179477735
Novex-1	7631	23116;23117;23118	chr2:178613010;178613009;178613008	chr2:179477737;179477736;179477735
Novex-2	7698	23317;23318;23319	chr2:178613010;178613009;178613008	chr2:179477737;179477736;179477735
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: Fn3-8
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.2426
• 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/H	None	None	None	N	0.277	0.091	0.0297737177859	gnomAD-4.0.0	1.59337E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43328E-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	0.1633	likely_benign	0.1173	benign	-0.996	Destabilizing	0.016	N	0.443	neutral	None	None	None	None	N
N/C	0.1945	likely_benign	0.1445	benign	-0.169	Destabilizing	0.676	D	0.605	neutral	None	None	None	None	N
N/D	0.1529	likely_benign	0.1665	benign	-1.164	Destabilizing	0.012	N	0.285	neutral	N	0.456990228	None	None	N
N/E	0.302	likely_benign	0.2884	benign	-0.991	Destabilizing	0.016	N	0.267	neutral	None	None	None	None	N
N/F	0.3325	likely_benign	0.2236	benign	-0.491	Destabilizing	0.214	N	0.6	neutral	None	None	None	None	N
N/G	0.2603	likely_benign	0.1947	benign	-1.397	Destabilizing	0.016	N	0.274	neutral	None	None	None	None	N
N/H	0.0865	likely_benign	0.0764	benign	-1.007	Destabilizing	None	N	0.277	neutral	N	0.435566118	None	None	N
N/I	0.1415	likely_benign	0.1121	benign	0.06	Stabilizing	0.029	N	0.549	neutral	N	0.451021006	None	None	N
N/K	0.375	ambiguous	0.3759	ambiguous	-0.339	Destabilizing	None	N	0.156	neutral	N	0.349456284	None	None	N
N/L	0.15	likely_benign	0.1105	benign	0.06	Stabilizing	0.016	N	0.433	neutral	None	None	None	None	N
N/M	0.2071	likely_benign	0.1471	benign	0.458	Stabilizing	0.003	N	0.429	neutral	None	None	None	None	N
N/P	0.8961	likely_pathogenic	0.8905	pathogenic	-0.263	Destabilizing	0.072	N	0.557	neutral	None	None	None	None	N
N/Q	0.2522	likely_benign	0.1989	benign	-0.924	Destabilizing	None	N	0.157	neutral	None	None	None	None	N
N/R	0.3656	ambiguous	0.3655	ambiguous	-0.478	Destabilizing	0.038	N	0.309	neutral	None	None	None	None	N
N/S	0.0698	likely_benign	0.0612	benign	-1.142	Destabilizing	None	N	0.164	neutral	N	0.358302894	None	None	N
N/T	0.0791	likely_benign	0.0632	benign	-0.772	Destabilizing	0.001	N	0.156	neutral	N	0.375891316	None	None	N
N/V	0.1562	likely_benign	0.1193	benign	-0.263	Destabilizing	0.016	N	0.423	neutral	None	None	None	None	N
N/W	0.5794	likely_pathogenic	0.5308	ambiguous	-0.277	Destabilizing	0.864	D	0.624	neutral	None	None	None	None	N
N/Y	0.133	likely_benign	0.1123	benign	-0.029	Destabilizing	0.093	N	0.593	neutral	N	0.478516327	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.