TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9457	28594;28595;28596	chr2:178710728;178710727;178710726	chr2:179575455;179575454;179575453
N2AB	9140	27643;27644;27645	chr2:178710728;178710727;178710726	chr2:179575455;179575454;179575453
N2A	8213	24862;24863;24864	chr2:178710728;178710727;178710726	chr2:179575455;179575454;179575453
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: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-80
• Domain position: 61
• Structural Position: 141
• Q(SASA): 0.3671
• 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/V	None	None	0.001	None	0.266	0.085	0.532168211543	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	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	0.2233	likely_benign	0.1942	benign	-1.037	Destabilizing	0.157	N	0.505	neutral	None	None	None	None	N
L/C	0.5714	likely_pathogenic	0.556	ambiguous	-0.853	Destabilizing	0.909	D	0.646	neutral	None	None	None	None	N
L/D	0.6538	likely_pathogenic	0.6051	pathogenic	-0.021	Destabilizing	0.567	D	0.699	prob.neutral	None	None	None	None	N
L/E	0.3154	likely_benign	0.2902	benign	-0.06	Destabilizing	0.567	D	0.679	prob.neutral	None	None	None	None	N
L/F	0.1374	likely_benign	0.1472	benign	-0.729	Destabilizing	0.331	N	0.511	neutral	None	None	None	None	N
L/G	0.4093	ambiguous	0.4089	ambiguous	-1.284	Destabilizing	0.567	D	0.607	neutral	None	None	None	None	N
L/H	0.2082	likely_benign	0.2232	benign	-0.425	Destabilizing	0.883	D	0.696	prob.neutral	None	None	None	None	N
L/I	0.1146	likely_benign	0.0829	benign	-0.475	Destabilizing	0.046	N	0.443	neutral	None	None	None	None	N
L/K	0.1872	likely_benign	0.2253	benign	-0.505	Destabilizing	0.567	D	0.591	neutral	None	None	None	None	N
L/M	0.1112	likely_benign	0.1066	benign	-0.478	Destabilizing	0.567	D	0.548	neutral	None	None	None	None	N
L/N	0.322	likely_benign	0.2791	benign	-0.327	Destabilizing	0.567	D	0.701	prob.neutral	None	None	None	None	N
L/P	0.3419	ambiguous	0.344	ambiguous	-0.628	Destabilizing	0.859	D	0.702	prob.neutral	None	None	None	None	N
L/Q	0.1015	likely_benign	0.116	benign	-0.515	Destabilizing	0.726	D	0.675	neutral	None	None	None	None	N
L/R	0.1442	likely_benign	0.171	benign	0.023	Stabilizing	0.667	D	0.673	neutral	None	None	None	None	N
L/S	0.2052	likely_benign	0.178	benign	-0.978	Destabilizing	0.033	N	0.356	neutral	None	None	None	None	N
L/T	0.184	likely_benign	0.1528	benign	-0.898	Destabilizing	0.157	N	0.541	neutral	None	None	None	None	N
L/V	0.1156	likely_benign	0.08	benign	-0.628	Destabilizing	0.001	N	0.266	neutral	None	None	None	None	N
L/W	0.2258	likely_benign	0.2673	benign	-0.708	Destabilizing	0.968	D	0.691	prob.neutral	None	None	None	None	N
L/Y	0.3692	ambiguous	0.3845	ambiguous	-0.472	Destabilizing	0.011	N	0.328	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.