TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16507	49744;49745;49746	chr2:178613764;178613763;178613762	chr2:179478491;179478490;179478489
N2AB	14866	44821;44822;44823	chr2:178613764;178613763;178613762	chr2:179478491;179478490;179478489
N2A	13939	42040;42041;42042	chr2:178613764;178613763;178613762	chr2:179478491;179478490;179478489
N2B	7442	22549;22550;22551	chr2:178613764;178613763;178613762	chr2:179478491;179478490;179478489
Novex-1	7567	22924;22925;22926	chr2:178613764;178613763;178613762	chr2:179478491;179478490;179478489
Novex-2	7634	23125;23126;23127	chr2:178613764;178613763;178613762	chr2:179478491;179478490;179478489
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-7
• Domain position: 58
• Structural Position: 88
• Q(SASA): 0.7056
• 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	0.411	0.229	0.281780670237	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
D/Y	None	None	1.0	N	0.687	0.458	0.529011059296	gnomAD-4.0.0	6.84825E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00121E-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
D/A	0.5829	likely_pathogenic	0.5039	ambiguous	0.009	Stabilizing	1.0	D	0.721	prob.delet.	N	0.471826134	None	None	I
D/C	0.9507	likely_pathogenic	0.8987	pathogenic	-0.11	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
D/E	0.3836	ambiguous	0.2385	benign	-0.242	Destabilizing	1.0	D	0.411	neutral	N	0.469188708	None	None	I
D/F	0.9303	likely_pathogenic	0.8965	pathogenic	0.337	Stabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	I
D/G	0.4412	ambiguous	0.3696	ambiguous	-0.22	Destabilizing	1.0	D	0.703	prob.neutral	N	0.475241841	None	None	I
D/H	0.8406	likely_pathogenic	0.7556	pathogenic	0.726	Stabilizing	1.0	D	0.664	neutral	N	0.472738625	None	None	I
D/I	0.8846	likely_pathogenic	0.863	pathogenic	0.571	Stabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
D/K	0.8857	likely_pathogenic	0.8328	pathogenic	0.502	Stabilizing	1.0	D	0.76	deleterious	None	None	None	None	I
D/L	0.8575	likely_pathogenic	0.7988	pathogenic	0.571	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
D/M	0.9322	likely_pathogenic	0.8845	pathogenic	0.409	Stabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
D/N	0.3035	likely_benign	0.2603	benign	-0.099	Destabilizing	1.0	D	0.593	neutral	N	0.476482206	None	None	I
D/P	0.9803	likely_pathogenic	0.9786	pathogenic	0.407	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
D/Q	0.8286	likely_pathogenic	0.7282	pathogenic	0.003	Stabilizing	1.0	D	0.662	neutral	None	None	None	None	I
D/R	0.9146	likely_pathogenic	0.8813	pathogenic	0.802	Stabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	I
D/S	0.4347	ambiguous	0.4004	ambiguous	-0.167	Destabilizing	1.0	D	0.631	neutral	None	None	None	None	I
D/T	0.6577	likely_pathogenic	0.5726	pathogenic	0.037	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
D/V	0.7169	likely_pathogenic	0.6815	pathogenic	0.407	Stabilizing	1.0	D	0.753	deleterious	N	0.482631177	None	None	I
D/W	0.9895	likely_pathogenic	0.982	pathogenic	0.496	Stabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	I
D/Y	0.6834	likely_pathogenic	0.608	pathogenic	0.604	Stabilizing	1.0	D	0.687	prob.neutral	N	0.517356552	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.