TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8442	25549;25550;25551	chr2:178717550;178717549;178717548	chr2:179582277;179582276;179582275
N2AB	8125	24598;24599;24600	chr2:178717550;178717549;178717548	chr2:179582277;179582276;179582275
N2A	7198	21817;21818;21819	chr2:178717550;178717549;178717548	chr2:179582277;179582276;179582275
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: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-69
• Domain position: 83
• Structural Position: 168
• Q(SASA): 0.3705
• Predicted PPI site: I

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/L	rs1560631528	None	0.998	N	0.61	0.325	None	gnomAD-2.1.1	4.07E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.99E-06	0
S/L	rs1560631528	None	0.998	N	0.61	0.325	None	gnomAD-4.0.0	2.74397E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.60529E-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	0.1006	likely_benign	0.1002	benign	-0.753	Destabilizing	0.724	D	0.497	neutral	N	0.492987392	None	None	I
S/C	0.2426	likely_benign	0.2181	benign	-0.384	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	I
S/D	0.5946	likely_pathogenic	0.5905	pathogenic	0.154	Stabilizing	0.983	D	0.473	neutral	None	None	None	None	I
S/E	0.6715	likely_pathogenic	0.6535	pathogenic	0.071	Stabilizing	0.681	D	0.313	neutral	None	None	None	None	I
S/F	0.1727	likely_benign	0.1656	benign	-1.333	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	I
S/G	0.1656	likely_benign	0.1596	benign	-0.874	Destabilizing	0.998	D	0.499	neutral	None	None	None	None	I
S/H	0.4241	ambiguous	0.3996	ambiguous	-1.4	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	I
S/I	0.1987	likely_benign	0.1977	benign	-0.556	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
S/K	0.7926	likely_pathogenic	0.7797	pathogenic	-0.528	Destabilizing	0.851	D	0.315	neutral	None	None	None	None	I
S/L	0.1245	likely_benign	0.1252	benign	-0.556	Destabilizing	0.998	D	0.61	neutral	N	0.493836766	None	None	I
S/M	0.2659	likely_benign	0.2651	benign	-0.117	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	I
S/N	0.2003	likely_benign	0.2021	benign	-0.253	Destabilizing	0.964	D	0.505	neutral	None	None	None	None	I
S/P	0.8078	likely_pathogenic	0.8013	pathogenic	-0.594	Destabilizing	0.999	D	0.678	prob.neutral	D	0.539844645	None	None	I
S/Q	0.5812	likely_pathogenic	0.5563	ambiguous	-0.538	Destabilizing	0.999	D	0.506	neutral	None	None	None	None	I
S/R	0.6873	likely_pathogenic	0.6588	pathogenic	-0.328	Destabilizing	0.999	D	0.638	neutral	None	None	None	None	I
S/T	0.0884	likely_benign	0.0893	benign	-0.412	Destabilizing	0.953	D	0.499	neutral	N	0.493941009	None	None	I
S/V	0.1878	likely_benign	0.1905	benign	-0.594	Destabilizing	0.999	D	0.633	neutral	None	None	None	None	I
S/W	0.4335	ambiguous	0.4035	ambiguous	-1.255	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
S/Y	0.2184	likely_benign	0.2068	benign	-1.01	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	I

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.