TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32676	98251;98252;98253	chr2:178540140;178540139;178540138	chr2:179404867;179404866;179404865
N2AB	31035	93328;93329;93330	chr2:178540140;178540139;178540138	chr2:179404867;179404866;179404865
N2A	30108	90547;90548;90549	chr2:178540140;178540139;178540138	chr2:179404867;179404866;179404865
N2B	23611	71056;71057;71058	chr2:178540140;178540139;178540138	chr2:179404867;179404866;179404865
Novex-1	23736	71431;71432;71433	chr2:178540140;178540139;178540138	chr2:179404867;179404866;179404865
Novex-2	23803	71632;71633;71634	chr2:178540140;178540139;178540138	chr2:179404867;179404866;179404865
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: Fn3-126
• Domain position: 77
• Structural Position: 109
• Q(SASA): 0.1416
• 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/I	None	None	0.013	N	0.489	0.081	0.33835085245	gnomAD-4.0.0	1.36894E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.31949E-05	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	0.2759	likely_benign	0.2756	benign	-2.795	Highly Destabilizing	0.404	N	0.714	prob.delet.	None	None	None	None	N
L/C	0.4318	ambiguous	0.4429	ambiguous	-2.03	Highly Destabilizing	0.991	D	0.769	deleterious	None	None	None	None	N
L/D	0.883	likely_pathogenic	0.9073	pathogenic	-3.277	Highly Destabilizing	0.906	D	0.862	deleterious	None	None	None	None	N
L/E	0.4967	ambiguous	0.5434	ambiguous	-3.117	Highly Destabilizing	0.906	D	0.831	deleterious	None	None	None	None	N
L/F	0.1503	likely_benign	0.1725	benign	-1.656	Destabilizing	0.826	D	0.736	prob.delet.	None	None	None	None	N
L/G	0.6825	likely_pathogenic	0.6975	pathogenic	-3.253	Highly Destabilizing	0.906	D	0.825	deleterious	None	None	None	None	N
L/H	0.2696	likely_benign	0.3145	benign	-2.595	Highly Destabilizing	0.991	D	0.823	deleterious	None	None	None	None	N
L/I	0.0987	likely_benign	0.0976	benign	-1.479	Destabilizing	0.013	N	0.489	neutral	N	0.430361172	None	None	N
L/K	0.2902	likely_benign	0.3701	ambiguous	-2.255	Highly Destabilizing	0.826	D	0.786	deleterious	None	None	None	None	N
L/M	0.0831	likely_benign	0.0809	benign	-1.384	Destabilizing	0.04	N	0.462	neutral	None	None	None	None	N
L/N	0.5491	ambiguous	0.5731	pathogenic	-2.44	Highly Destabilizing	0.906	D	0.865	deleterious	None	None	None	None	N
L/P	0.9804	likely_pathogenic	0.9851	pathogenic	-1.9	Destabilizing	0.957	D	0.861	deleterious	N	0.520385743	None	None	N
L/Q	0.175	likely_benign	0.1938	benign	-2.413	Highly Destabilizing	0.782	D	0.829	deleterious	N	0.459102424	None	None	N
L/R	0.2279	likely_benign	0.2953	benign	-1.75	Destabilizing	0.782	D	0.807	deleterious	N	0.401056985	None	None	N
L/S	0.2909	likely_benign	0.2862	benign	-3.036	Highly Destabilizing	0.826	D	0.751	deleterious	None	None	None	None	N
L/T	0.1751	likely_benign	0.1777	benign	-2.764	Highly Destabilizing	0.826	D	0.76	deleterious	None	None	None	None	N
L/V	0.0931	likely_benign	0.0956	benign	-1.9	Destabilizing	0.013	N	0.505	neutral	N	0.427955585	None	None	N
L/W	0.3217	likely_benign	0.3931	ambiguous	-2.031	Highly Destabilizing	0.991	D	0.775	deleterious	None	None	None	None	N
L/Y	0.3576	ambiguous	0.4126	ambiguous	-1.856	Destabilizing	0.906	D	0.799	deleterious	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.