TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9258	27997;27998;27999	chr2:178712058;178712057;178712056	chr2:179576785;179576784;179576783
N2AB	8941	27046;27047;27048	chr2:178712058;178712057;178712056	chr2:179576785;179576784;179576783
N2A	8014	24265;24266;24267	chr2:178712058;178712057;178712056	chr2:179576785;179576784;179576783
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-78
• Domain position: 54
• Structural Position: 134
• Q(SASA): 0.4693
• 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/K	rs749135942	0.216	0.379	N	0.271	0.123	0.165133752707	gnomAD-2.1.1	1.2E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	9.28E-05	8.86E-06	0
N/K	rs749135942	0.216	0.379	N	0.271	0.123	0.165133752707	gnomAD-4.0.0	2.73685E-06	None	None	None	None	N	None	0	0	None	0	0	None	5.6184E-05	0	0	0	1.65673E-05
N/T	None	None	0.549	N	0.283	0.226	0.376216005999	gnomAD-4.0.0	1.36843E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79896E-06	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
N/A	0.4722	ambiguous	0.5419	ambiguous	-0.823	Destabilizing	0.25	N	0.416	neutral	None	None	None	None	N
N/C	0.5044	ambiguous	0.6388	pathogenic	-0.018	Destabilizing	0.992	D	0.513	neutral	None	None	None	None	N
N/D	0.1754	likely_benign	0.2232	benign	-0.265	Destabilizing	0.549	D	0.266	neutral	N	0.489844698	None	None	N
N/E	0.5983	likely_pathogenic	0.6375	pathogenic	-0.137	Destabilizing	0.447	N	0.245	neutral	None	None	None	None	N
N/F	0.8171	likely_pathogenic	0.8453	pathogenic	-0.57	Destabilizing	0.85	D	0.509	neutral	None	None	None	None	N
N/G	0.3206	likely_benign	0.3831	ambiguous	-1.177	Destabilizing	0.001	N	0.129	neutral	None	None	None	None	N
N/H	0.1478	likely_benign	0.1896	benign	-0.743	Destabilizing	0.009	N	0.17	neutral	D	0.534945056	None	None	N
N/I	0.6861	likely_pathogenic	0.7605	pathogenic	0.088	Stabilizing	0.896	D	0.514	neutral	N	0.515877813	None	None	N
N/K	0.4573	ambiguous	0.5091	ambiguous	-0.058	Destabilizing	0.379	N	0.271	neutral	N	0.517319301	None	None	N
N/L	0.5643	likely_pathogenic	0.5912	pathogenic	0.088	Stabilizing	0.617	D	0.478	neutral	None	None	None	None	N
N/M	0.6181	likely_pathogenic	0.6621	pathogenic	0.312	Stabilizing	0.977	D	0.469	neutral	None	None	None	None	N
N/P	0.9245	likely_pathogenic	0.9412	pathogenic	-0.186	Destabilizing	0.92	D	0.467	neutral	None	None	None	None	N
N/Q	0.4436	ambiguous	0.4757	ambiguous	-0.617	Destabilizing	0.021	N	0.185	neutral	None	None	None	None	N
N/R	0.4565	ambiguous	0.5142	ambiguous	-0.117	Destabilizing	0.447	N	0.367	neutral	None	None	None	None	N
N/S	0.1106	likely_benign	0.1302	benign	-0.823	Destabilizing	0.334	N	0.303	neutral	N	0.483284085	None	None	N
N/T	0.3205	likely_benign	0.3585	ambiguous	-0.486	Destabilizing	0.549	D	0.283	neutral	N	0.517455373	None	None	N
N/V	0.6856	likely_pathogenic	0.7546	pathogenic	-0.186	Destabilizing	0.92	D	0.483	neutral	None	None	None	None	N
N/W	0.9062	likely_pathogenic	0.9379	pathogenic	-0.344	Destabilizing	0.992	D	0.526	neutral	None	None	None	None	N
N/Y	0.324	likely_benign	0.3836	ambiguous	-0.1	Destabilizing	0.681	D	0.486	neutral	D	0.529827238	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.