TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20192	60799;60800;60801	chr2:178591151;178591150;178591149	chr2:179455878;179455877;179455876
N2AB	18551	55876;55877;55878	chr2:178591151;178591150;178591149	chr2:179455878;179455877;179455876
N2A	17624	53095;53096;53097	chr2:178591151;178591150;178591149	chr2:179455878;179455877;179455876
N2B	11127	33604;33605;33606	chr2:178591151;178591150;178591149	chr2:179455878;179455877;179455876
Novex-1	11252	33979;33980;33981	chr2:178591151;178591150;178591149	chr2:179455878;179455877;179455876
Novex-2	11319	34180;34181;34182	chr2:178591151;178591150;178591149	chr2:179455878;179455877;179455876
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-34
• Domain position: 22
• Structural Position: 23
• Q(SASA): 0.1767
• 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
S/P	None	None	0.492	N	0.543	0.371	0.423119698836	gnomAD-4.0.0	1.59227E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85999E-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
S/A	0.0946	likely_benign	0.093	benign	-0.63	Destabilizing	0.001	N	0.191	neutral	N	0.506056583	None	None	N
S/C	0.1103	likely_benign	0.0992	benign	-0.379	Destabilizing	0.944	D	0.563	neutral	None	None	None	None	N
S/D	0.5599	ambiguous	0.554	ambiguous	-1.077	Destabilizing	0.002	N	0.172	neutral	None	None	None	None	N
S/E	0.5709	likely_pathogenic	0.5269	ambiguous	-0.909	Destabilizing	0.004	N	0.179	neutral	None	None	None	None	N
S/F	0.2341	likely_benign	0.2281	benign	-0.423	Destabilizing	0.818	D	0.63	neutral	None	None	None	None	N
S/G	0.1527	likely_benign	0.1639	benign	-1.025	Destabilizing	0.116	N	0.367	neutral	None	None	None	None	N
S/H	0.3638	ambiguous	0.3321	benign	-1.435	Destabilizing	0.932	D	0.578	neutral	None	None	None	None	N
S/I	0.2233	likely_benign	0.2053	benign	0.36	Stabilizing	0.69	D	0.596	neutral	None	None	None	None	N
S/K	0.74	likely_pathogenic	0.7325	pathogenic	-0.316	Destabilizing	0.388	N	0.409	neutral	None	None	None	None	N
S/L	0.1119	likely_benign	0.1063	benign	0.36	Stabilizing	0.193	N	0.514	neutral	N	0.521756754	None	None	N
S/M	0.2204	likely_benign	0.1877	benign	0.285	Stabilizing	0.944	D	0.568	neutral	None	None	None	None	N
S/N	0.2113	likely_benign	0.1993	benign	-0.876	Destabilizing	0.388	N	0.458	neutral	None	None	None	None	N
S/P	0.9677	likely_pathogenic	0.9812	pathogenic	0.067	Stabilizing	0.492	N	0.543	neutral	N	0.516676464	None	None	N
S/Q	0.5011	ambiguous	0.452	ambiguous	-0.652	Destabilizing	0.388	N	0.478	neutral	None	None	None	None	N
S/R	0.6145	likely_pathogenic	0.63	pathogenic	-0.661	Destabilizing	0.69	D	0.549	neutral	None	None	None	None	N
S/T	0.101	likely_benign	0.0944	benign	-0.575	Destabilizing	0.165	N	0.407	neutral	N	0.448739076	None	None	N
S/V	0.2453	likely_benign	0.2168	benign	0.067	Stabilizing	0.241	N	0.515	neutral	None	None	None	None	N
S/W	0.3729	ambiguous	0.3697	ambiguous	-0.694	Destabilizing	0.981	D	0.718	prob.delet.	None	None	None	None	N
S/Y	0.2198	likely_benign	0.2103	benign	-0.247	Destabilizing	0.932	D	0.628	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.