TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24150	72673;72674;72675	chr2:178573684;178573683;178573682	chr2:179438411;179438410;179438409
N2AB	22509	67750;67751;67752	chr2:178573684;178573683;178573682	chr2:179438411;179438410;179438409
N2A	21582	64969;64970;64971	chr2:178573684;178573683;178573682	chr2:179438411;179438410;179438409
N2B	15085	45478;45479;45480	chr2:178573684;178573683;178573682	chr2:179438411;179438410;179438409
Novex-1	15210	45853;45854;45855	chr2:178573684;178573683;178573682	chr2:179438411;179438410;179438409
Novex-2	15277	46054;46055;46056	chr2:178573684;178573683;178573682	chr2:179438411;179438410;179438409
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-63
• Domain position: 29
• Structural Position: 30
• Q(SASA): 0.3576
• 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
D/E	None	None	1.0	N	0.443	0.301	0.422762650823	gnomAD-4.0.0	7.31337E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.36723E-07	0	0
D/N	None	None	1.0	N	0.713	0.374	0.443999229985	gnomAD-4.0.0	1.20034E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31252E-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
D/A	0.638	likely_pathogenic	0.7618	pathogenic	-0.252	Destabilizing	1.0	D	0.718	prob.delet.	N	0.496349574	None	None	I
D/C	0.9127	likely_pathogenic	0.9435	pathogenic	0.164	Stabilizing	1.0	D	0.655	neutral	None	None	None	None	I
D/E	0.6672	likely_pathogenic	0.7647	pathogenic	-0.593	Destabilizing	1.0	D	0.443	neutral	N	0.503400239	None	None	I
D/F	0.9361	likely_pathogenic	0.9637	pathogenic	-0.423	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	I
D/G	0.627	likely_pathogenic	0.7542	pathogenic	-0.502	Destabilizing	1.0	D	0.704	prob.neutral	N	0.512024747	None	None	I
D/H	0.7411	likely_pathogenic	0.8216	pathogenic	-0.749	Destabilizing	1.0	D	0.655	neutral	N	0.514555961	None	None	I
D/I	0.825	likely_pathogenic	0.8939	pathogenic	0.366	Stabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	I
D/K	0.8742	likely_pathogenic	0.9323	pathogenic	0.068	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
D/L	0.8701	likely_pathogenic	0.9174	pathogenic	0.366	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
D/M	0.9166	likely_pathogenic	0.957	pathogenic	0.779	Stabilizing	1.0	D	0.645	neutral	None	None	None	None	I
D/N	0.1389	likely_benign	0.1568	benign	-0.176	Destabilizing	1.0	D	0.713	prob.delet.	N	0.469282097	None	None	I
D/P	0.9618	likely_pathogenic	0.9755	pathogenic	0.184	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
D/Q	0.8432	likely_pathogenic	0.9101	pathogenic	-0.115	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
D/R	0.8766	likely_pathogenic	0.9298	pathogenic	0.018	Stabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
D/S	0.2875	likely_benign	0.401	ambiguous	-0.307	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	I
D/T	0.4512	ambiguous	0.6266	pathogenic	-0.113	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
D/V	0.6861	likely_pathogenic	0.7911	pathogenic	0.184	Stabilizing	1.0	D	0.696	prob.neutral	D	0.523759446	None	None	I
D/W	0.9899	likely_pathogenic	0.9936	pathogenic	-0.407	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	I
D/Y	0.6977	likely_pathogenic	0.7983	pathogenic	-0.221	Destabilizing	1.0	D	0.629	neutral	D	0.528647745	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.