TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6770	20533;20534;20535	chr2:178726014;178726013;178726012	chr2:179590741;179590740;179590739
N2AB	6453	19582;19583;19584	chr2:178726014;178726013;178726012	chr2:179590741;179590740;179590739
N2A	5526	16801;16802;16803	chr2:178726014;178726013;178726012	chr2:179590741;179590740;179590739
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: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-52
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.2347
• 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
V/A	None	None	0.007	N	0.107	0.156	0.497613835824	gnomAD-4.0.0	1.74383E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.6619E-05	0
V/I	None	None	0.003	N	0.162	0.136	0.421427970867	gnomAD-4.0.0	7.12211E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.25799E-07	0	0
V/L	None	None	0.001	N	0.099	0.136	0.340510301474	gnomAD-4.0.0	2.84884E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.7032E-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
V/A	0.1381	likely_benign	0.1281	benign	-1.551	Destabilizing	0.007	N	0.107	neutral	N	0.517074158	None	None	N
V/C	0.7223	likely_pathogenic	0.7183	pathogenic	-1.06	Destabilizing	0.998	D	0.34	neutral	None	None	None	None	N
V/D	0.4593	ambiguous	0.4626	ambiguous	-1.415	Destabilizing	0.992	D	0.444	neutral	None	None	None	None	N
V/E	0.301	likely_benign	0.2714	benign	-1.371	Destabilizing	0.677	D	0.382	neutral	N	0.513567771	None	None	N
V/F	0.1507	likely_benign	0.1474	benign	-1.054	Destabilizing	0.978	D	0.349	neutral	None	None	None	None	N
V/G	0.2482	likely_benign	0.2445	benign	-1.923	Destabilizing	0.898	D	0.42	neutral	N	0.513314281	None	None	N
V/H	0.5044	ambiguous	0.4934	ambiguous	-1.57	Destabilizing	0.999	D	0.442	neutral	None	None	None	None	N
V/I	0.0747	likely_benign	0.0734	benign	-0.61	Destabilizing	0.003	N	0.162	neutral	N	0.512070983	None	None	N
V/K	0.3026	likely_benign	0.2824	benign	-1.41	Destabilizing	0.752	D	0.385	neutral	None	None	None	None	N
V/L	0.1662	likely_benign	0.1475	benign	-0.61	Destabilizing	0.001	N	0.099	neutral	N	0.515225932	None	None	N
V/M	0.1267	likely_benign	0.11	benign	-0.503	Destabilizing	0.97	D	0.368	neutral	None	None	None	None	N
V/N	0.3437	ambiguous	0.3417	ambiguous	-1.232	Destabilizing	0.865	D	0.456	neutral	None	None	None	None	N
V/P	0.597	likely_pathogenic	0.5781	pathogenic	-0.889	Destabilizing	0.865	D	0.412	neutral	None	None	None	None	N
V/Q	0.2711	likely_benign	0.2519	benign	-1.318	Destabilizing	0.968	D	0.411	neutral	None	None	None	None	N
V/R	0.2548	likely_benign	0.2545	benign	-0.994	Destabilizing	0.286	N	0.353	neutral	None	None	None	None	N
V/S	0.2143	likely_benign	0.2059	benign	-1.781	Destabilizing	0.777	D	0.382	neutral	None	None	None	None	N
V/T	0.1327	likely_benign	0.1256	benign	-1.622	Destabilizing	0.738	D	0.303	neutral	None	None	None	None	N
V/W	0.7396	likely_pathogenic	0.7283	pathogenic	-1.332	Destabilizing	1.0	D	0.511	neutral	None	None	None	None	N
V/Y	0.5152	ambiguous	0.4939	ambiguous	-1.022	Destabilizing	0.989	D	0.354	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.