TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33031	99316;99317;99318	chr2:178538738;178538737;178538736	chr2:179403465;179403464;179403463
N2AB	31390	94393;94394;94395	chr2:178538738;178538737;178538736	chr2:179403465;179403464;179403463
N2A	30463	91612;91613;91614	chr2:178538738;178538737;178538736	chr2:179403465;179403464;179403463
N2B	23966	72121;72122;72123	chr2:178538738;178538737;178538736	chr2:179403465;179403464;179403463
Novex-1	24091	72496;72497;72498	chr2:178538738;178538737;178538736	chr2:179403465;179403464;179403463
Novex-2	24158	72697;72698;72699	chr2:178538738;178538737;178538736	chr2:179403465;179403464;179403463
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-129
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.4156
• 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	0.1	N	0.206	0.053	0.40749426699	gnomAD-4.0.0	1.59141E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43287E-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	0.1693	likely_benign	0.1872	benign	-0.953	Destabilizing	0.953	D	0.531	neutral	None	None	None	None	N
L/C	0.5167	ambiguous	0.5354	ambiguous	-0.589	Destabilizing	0.999	D	0.72	prob.delet.	None	None	None	None	N
L/D	0.7071	likely_pathogenic	0.7141	pathogenic	-0.468	Destabilizing	0.986	D	0.82	deleterious	None	None	None	None	N
L/E	0.3376	likely_benign	0.3355	benign	-0.54	Destabilizing	0.973	D	0.734	prob.delet.	None	None	None	None	N
L/F	0.1917	likely_benign	0.2239	benign	-0.769	Destabilizing	0.982	D	0.656	neutral	N	0.488778704	None	None	N
L/G	0.5181	ambiguous	0.5617	ambiguous	-1.172	Destabilizing	0.993	D	0.819	deleterious	None	None	None	None	N
L/H	0.2425	likely_benign	0.2663	benign	-0.385	Destabilizing	0.998	D	0.788	deleterious	N	0.480638403	None	None	N
L/I	0.0843	likely_benign	0.0848	benign	-0.474	Destabilizing	0.1	N	0.206	neutral	N	0.480059273	None	None	N
L/K	0.2777	likely_benign	0.2687	benign	-0.606	Destabilizing	0.973	D	0.708	prob.delet.	None	None	None	None	N
L/M	0.1131	likely_benign	0.1203	benign	-0.41	Destabilizing	0.986	D	0.653	neutral	None	None	None	None	N
L/N	0.3493	ambiguous	0.3788	ambiguous	-0.305	Destabilizing	0.993	D	0.822	deleterious	None	None	None	None	N
L/P	0.8219	likely_pathogenic	0.8474	pathogenic	-0.6	Destabilizing	0.997	D	0.82	deleterious	N	0.495615559	None	None	N
L/Q	0.1271	likely_benign	0.1406	benign	-0.55	Destabilizing	0.807	D	0.435	neutral	None	None	None	None	N
L/R	0.2129	likely_benign	0.2215	benign	0.017	Stabilizing	0.982	D	0.792	deleterious	N	0.487254605	None	None	N
L/S	0.1947	likely_benign	0.2116	benign	-0.8	Destabilizing	0.986	D	0.671	neutral	None	None	None	None	N
L/T	0.1074	likely_benign	0.1063	benign	-0.764	Destabilizing	0.986	D	0.673	neutral	None	None	None	None	N
L/V	0.0892	likely_benign	0.0924	benign	-0.6	Destabilizing	0.76	D	0.495	neutral	N	0.494641937	None	None	N
L/W	0.4029	ambiguous	0.4409	ambiguous	-0.774	Destabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
L/Y	0.4642	ambiguous	0.5249	ambiguous	-0.557	Destabilizing	0.998	D	0.759	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.