TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8165	24718;24719;24720	chr2:178718707;178718706;178718705	chr2:179583434;179583433;179583432
N2AB	7848	23767;23768;23769	chr2:178718707;178718706;178718705	chr2:179583434;179583433;179583432
N2A	6921	20986;20987;20988	chr2:178718707;178718706;178718705	chr2:179583434;179583433;179583432
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-66
• Domain position: 88
• Structural Position: 174
• Q(SASA): 0.051
• 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	rs1060500582	None	0.996	N	0.603	0.35	0.506793516358	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.93648E-04	None	0	0	0	0	0
L/I	rs1060500582	None	0.996	N	0.603	0.35	0.506793516358	gnomAD-4.0.0	1.85968E-06	None	None	None	None	N	None	0	0	None	0	2.22975E-05	None	0	0	8.47828E-07	0	1.60149E-05
L/P	None	None	1.0	D	0.905	0.747	0.892836903121	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
L/V	None	None	0.996	N	0.606	0.348	0.485348376517	gnomAD-4.0.0	6.844E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99683E-07	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	0.8102	likely_pathogenic	0.8308	pathogenic	-2.606	Highly Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	N
L/C	0.8113	likely_pathogenic	0.8109	pathogenic	-1.9	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
L/D	0.9986	likely_pathogenic	0.9991	pathogenic	-3.0	Highly Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
L/E	0.9922	likely_pathogenic	0.9948	pathogenic	-2.664	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
L/F	0.5514	ambiguous	0.6194	pathogenic	-1.635	Destabilizing	0.64	D	0.459	neutral	N	0.517503066	None	None	N
L/G	0.9711	likely_pathogenic	0.9764	pathogenic	-3.244	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
L/H	0.9634	likely_pathogenic	0.9747	pathogenic	-3.041	Highly Destabilizing	1.0	D	0.895	deleterious	D	0.548231074	None	None	N
L/I	0.1168	likely_benign	0.1299	benign	-0.692	Destabilizing	0.996	D	0.603	neutral	N	0.497913873	None	None	N
L/K	0.9869	likely_pathogenic	0.9901	pathogenic	-1.905	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
L/M	0.3382	likely_benign	0.3663	ambiguous	-0.872	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
L/N	0.9881	likely_pathogenic	0.9921	pathogenic	-2.612	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
L/P	0.9922	likely_pathogenic	0.9933	pathogenic	-1.32	Destabilizing	1.0	D	0.905	deleterious	D	0.548231074	None	None	N
L/Q	0.9566	likely_pathogenic	0.9695	pathogenic	-2.206	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
L/R	0.9562	likely_pathogenic	0.9668	pathogenic	-2.082	Highly Destabilizing	1.0	D	0.899	deleterious	D	0.548231074	None	None	N
L/S	0.9615	likely_pathogenic	0.9727	pathogenic	-3.247	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
L/T	0.8715	likely_pathogenic	0.9022	pathogenic	-2.727	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
L/V	0.117	likely_benign	0.1244	benign	-1.32	Destabilizing	0.996	D	0.606	neutral	N	0.480006519	None	None	N
L/W	0.9417	likely_pathogenic	0.9563	pathogenic	-2.006	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
L/Y	0.9348	likely_pathogenic	0.9454	pathogenic	-1.758	Destabilizing	0.998	D	0.871	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.