TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28179	84760;84761;84762	chr2:178561597;178561596;178561595	chr2:179426324;179426323;179426322
N2AB	26538	79837;79838;79839	chr2:178561597;178561596;178561595	chr2:179426324;179426323;179426322
N2A	25611	77056;77057;77058	chr2:178561597;178561596;178561595	chr2:179426324;179426323;179426322
N2B	19114	57565;57566;57567	chr2:178561597;178561596;178561595	chr2:179426324;179426323;179426322
Novex-1	19239	57940;57941;57942	chr2:178561597;178561596;178561595	chr2:179426324;179426323;179426322
Novex-2	19306	58141;58142;58143	chr2:178561597;178561596;178561595	chr2:179426324;179426323;179426322
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-93
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.9175
• 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
V/I	None	None	0.645	N	0.449	0.166	0.399889258716	gnomAD-4.0.0	1.36898E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99654E-07	0	1.65717E-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
V/A	0.3041	likely_benign	0.3013	benign	-0.316	Destabilizing	0.012	N	0.109	neutral	N	0.43293733	None	None	I
V/C	0.7831	likely_pathogenic	0.7922	pathogenic	-0.706	Destabilizing	0.996	D	0.376	neutral	None	None	None	None	I
V/D	0.6221	likely_pathogenic	0.6149	pathogenic	-0.412	Destabilizing	0.521	D	0.443	neutral	N	0.488945329	None	None	I
V/E	0.5149	ambiguous	0.5009	ambiguous	-0.537	Destabilizing	0.009	N	0.252	neutral	None	None	None	None	I
V/F	0.3203	likely_benign	0.3197	benign	-0.695	Destabilizing	0.979	D	0.389	neutral	N	0.482849994	None	None	I
V/G	0.3128	likely_benign	0.3251	benign	-0.386	Destabilizing	0.521	D	0.442	neutral	N	0.489081402	None	None	I
V/H	0.7493	likely_pathogenic	0.7412	pathogenic	-0.015	Destabilizing	0.987	D	0.391	neutral	None	None	None	None	I
V/I	0.0937	likely_benign	0.0909	benign	-0.28	Destabilizing	0.645	D	0.449	neutral	N	0.464916463	None	None	I
V/K	0.5837	likely_pathogenic	0.5613	ambiguous	-0.394	Destabilizing	0.59	D	0.462	neutral	None	None	None	None	I
V/L	0.2713	likely_benign	0.2566	benign	-0.28	Destabilizing	0.472	N	0.485	neutral	N	0.477882973	None	None	I
V/M	0.2231	likely_benign	0.2223	benign	-0.487	Destabilizing	0.984	D	0.42	neutral	None	None	None	None	I
V/N	0.446	ambiguous	0.4551	ambiguous	-0.158	Destabilizing	0.91	D	0.437	neutral	None	None	None	None	I
V/P	0.603	likely_pathogenic	0.6087	pathogenic	-0.262	Destabilizing	0.953	D	0.418	neutral	None	None	None	None	I
V/Q	0.4866	ambiguous	0.4868	ambiguous	-0.399	Destabilizing	0.835	D	0.43	neutral	None	None	None	None	I
V/R	0.5006	ambiguous	0.4866	ambiguous	0.087	Stabilizing	0.91	D	0.437	neutral	None	None	None	None	I
V/S	0.3391	likely_benign	0.3458	ambiguous	-0.443	Destabilizing	0.59	D	0.425	neutral	None	None	None	None	I
V/T	0.3382	likely_benign	0.3431	ambiguous	-0.477	Destabilizing	0.742	D	0.421	neutral	None	None	None	None	I
V/W	0.8887	likely_pathogenic	0.8886	pathogenic	-0.763	Destabilizing	0.996	D	0.513	neutral	None	None	None	None	I
V/Y	0.6862	likely_pathogenic	0.6816	pathogenic	-0.476	Destabilizing	0.984	D	0.381	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.