TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26379	79360;79361;79362	chr2:178566997;178566996;178566995	chr2:179431724;179431723;179431722
N2AB	24738	74437;74438;74439	chr2:178566997;178566996;178566995	chr2:179431724;179431723;179431722
N2A	23811	71656;71657;71658	chr2:178566997;178566996;178566995	chr2:179431724;179431723;179431722
N2B	17314	52165;52166;52167	chr2:178566997;178566996;178566995	chr2:179431724;179431723;179431722
Novex-1	17439	52540;52541;52542	chr2:178566997;178566996;178566995	chr2:179431724;179431723;179431722
Novex-2	17506	52741;52742;52743	chr2:178566997;178566996;178566995	chr2:179431724;179431723;179431722
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-79
• Domain position: 94
• Structural Position: 129
• Q(SASA): 0.3622
• 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
L/R	None	None	0.8	N	0.635	0.413	0.772253545797	gnomAD-4.0.0	1.36854E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99552E-07	0	1.65717E-05
L/V	rs1706131161	None	0.001	N	0.196	0.039	0.208816687407	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/V	rs1706131161	None	0.001	N	0.196	0.039	0.208816687407	gnomAD-4.0.0	6.57713E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47054E-05	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
L/A	0.2085	likely_benign	0.2058	benign	-1.253	Destabilizing	0.134	N	0.428	neutral	None	None	None	None	N
L/C	0.3827	ambiguous	0.3953	ambiguous	-0.706	Destabilizing	0.984	D	0.489	neutral	None	None	None	None	N
L/D	0.7131	likely_pathogenic	0.7022	pathogenic	-0.76	Destabilizing	0.942	D	0.693	prob.delet.	None	None	None	None	N
L/E	0.3455	ambiguous	0.3424	ambiguous	-0.805	Destabilizing	0.842	D	0.677	prob.neutral	None	None	None	None	N
L/F	0.1424	likely_benign	0.1322	benign	-0.955	Destabilizing	0.724	D	0.44	neutral	None	None	None	None	N
L/G	0.5685	likely_pathogenic	0.5367	ambiguous	-1.512	Destabilizing	0.842	D	0.665	prob.neutral	None	None	None	None	N
L/H	0.2225	likely_benign	0.218	benign	-0.677	Destabilizing	0.984	D	0.667	prob.neutral	None	None	None	None	N
L/I	0.0711	likely_benign	0.0749	benign	-0.648	Destabilizing	0.001	N	0.22	neutral	N	0.412868702	None	None	N
L/K	0.2164	likely_benign	0.2227	benign	-0.828	Destabilizing	0.724	D	0.605	neutral	None	None	None	None	N
L/M	0.09	likely_benign	0.0828	benign	-0.488	Destabilizing	0.063	N	0.295	neutral	None	None	None	None	N
L/N	0.3743	ambiguous	0.3692	ambiguous	-0.598	Destabilizing	0.942	D	0.684	prob.delet.	None	None	None	None	N
L/P	0.3665	ambiguous	0.3862	ambiguous	-0.817	Destabilizing	0.924	D	0.693	prob.delet.	N	0.470719994	None	None	N
L/Q	0.1328	likely_benign	0.1303	benign	-0.825	Destabilizing	0.8	D	0.629	neutral	N	0.481733904	None	None	N
L/R	0.1865	likely_benign	0.1872	benign	-0.171	Destabilizing	0.8	D	0.635	neutral	N	0.481226925	None	None	N
L/S	0.2772	likely_benign	0.2615	benign	-1.121	Destabilizing	0.428	N	0.539	neutral	None	None	None	None	N
L/T	0.1503	likely_benign	0.1543	benign	-1.056	Destabilizing	0.428	N	0.465	neutral	None	None	None	None	N
L/V	0.0681	likely_benign	0.0706	benign	-0.817	Destabilizing	0.001	N	0.196	neutral	N	0.432550541	None	None	N
L/W	0.2968	likely_benign	0.2789	benign	-0.988	Destabilizing	0.984	D	0.658	prob.neutral	None	None	None	None	N
L/Y	0.339	likely_benign	0.3248	benign	-0.771	Destabilizing	0.842	D	0.514	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.