TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30624	92095;92096;92097	chr2:178549852;178549851;178549850	chr2:179414579;179414578;179414577
N2AB	28983	87172;87173;87174	chr2:178549852;178549851;178549850	chr2:179414579;179414578;179414577
N2A	28056	84391;84392;84393	chr2:178549852;178549851;178549850	chr2:179414579;179414578;179414577
N2B	21559	64900;64901;64902	chr2:178549852;178549851;178549850	chr2:179414579;179414578;179414577
Novex-1	21684	65275;65276;65277	chr2:178549852;178549851;178549850	chr2:179414579;179414578;179414577
Novex-2	21751	65476;65477;65478	chr2:178549852;178549851;178549850	chr2:179414579;179414578;179414577
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: Fn3-111
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.2294
• 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	rs886055231	None	0.139	N	0.269	0.061	0.233785782151	gnomAD-4.0.0	2.81307E-06	None	None	None	None	N	None	0	7.78291E-05	None	0	0	None	0	0	9.14608E-07	0	0
V/I	rs1474057900	None	0.425	N	0.315	0.114	0.227260227426	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/I	rs1474057900	None	0.425	N	0.315	0.114	0.227260227426	gnomAD-4.0.0	6.57151E-06	None	None	None	None	N	None	2.41301E-05	0	None	0	0	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
V/A	0.067	likely_benign	0.0726	benign	-1.237	Destabilizing	0.139	N	0.269	neutral	N	0.439950942	None	None	N
V/C	0.4999	ambiguous	0.5425	ambiguous	-0.786	Destabilizing	0.995	D	0.344	neutral	None	None	None	None	N
V/D	0.2101	likely_benign	0.2355	benign	-0.996	Destabilizing	0.002	N	0.393	neutral	N	0.440991092	None	None	N
V/E	0.155	likely_benign	0.168	benign	-1.018	Destabilizing	0.004	N	0.257	neutral	None	None	None	None	N
V/F	0.1631	likely_benign	0.1835	benign	-0.966	Destabilizing	0.975	D	0.395	neutral	N	0.499903323	None	None	N
V/G	0.1096	likely_benign	0.1141	benign	-1.521	Destabilizing	0.001	N	0.358	neutral	N	0.481144204	None	None	N
V/H	0.3878	ambiguous	0.4224	ambiguous	-1.027	Destabilizing	0.981	D	0.44	neutral	None	None	None	None	N
V/I	0.0775	likely_benign	0.0817	benign	-0.573	Destabilizing	0.425	N	0.315	neutral	N	0.469407058	None	None	N
V/K	0.194	likely_benign	0.2117	benign	-1.101	Destabilizing	0.495	N	0.305	neutral	None	None	None	None	N
V/L	0.1453	likely_benign	0.1512	benign	-0.573	Destabilizing	0.425	N	0.278	neutral	N	0.468713624	None	None	N
V/M	0.119	likely_benign	0.1296	benign	-0.458	Destabilizing	0.981	D	0.377	neutral	None	None	None	None	N
V/N	0.1735	likely_benign	0.1807	benign	-0.841	Destabilizing	0.495	N	0.369	neutral	None	None	None	None	N
V/P	0.4466	ambiguous	0.4721	ambiguous	-0.759	Destabilizing	0.936	D	0.397	neutral	None	None	None	None	N
V/Q	0.1964	likely_benign	0.2059	benign	-1.018	Destabilizing	0.704	D	0.397	neutral	None	None	None	None	N
V/R	0.1792	likely_benign	0.1991	benign	-0.555	Destabilizing	0.704	D	0.449	neutral	None	None	None	None	N
V/S	0.0971	likely_benign	0.1026	benign	-1.312	Destabilizing	0.329	N	0.342	neutral	None	None	None	None	N
V/T	0.0808	likely_benign	0.0885	benign	-1.226	Destabilizing	0.013	N	0.126	neutral	None	None	None	None	N
V/W	0.7082	likely_pathogenic	0.7715	pathogenic	-1.129	Destabilizing	0.995	D	0.444	neutral	None	None	None	None	N
V/Y	0.4503	ambiguous	0.49	ambiguous	-0.851	Destabilizing	0.981	D	0.375	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.