TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23267	70024;70025;70026	chr2:178576333;178576332;178576331	chr2:179441060;179441059;179441058
N2AB	21626	65101;65102;65103	chr2:178576333;178576332;178576331	chr2:179441060;179441059;179441058
N2A	20699	62320;62321;62322	chr2:178576333;178576332;178576331	chr2:179441060;179441059;179441058
N2B	14202	42829;42830;42831	chr2:178576333;178576332;178576331	chr2:179441060;179441059;179441058
Novex-1	14327	43204;43205;43206	chr2:178576333;178576332;178576331	chr2:179441060;179441059;179441058
Novex-2	14394	43405;43406;43407	chr2:178576333;178576332;178576331	chr2:179441060;179441059;179441058
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: Fn3-57
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.3369
• 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/H	None	None	1.0	N	0.649	0.413	0.382087116544	gnomAD-4.0.0	1.71681E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.0149E-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	0.8507	likely_pathogenic	0.8365	pathogenic	-0.688	Destabilizing	1.0	D	0.73	prob.delet.	N	0.49141205	None	None	I
D/C	0.9652	likely_pathogenic	0.9619	pathogenic	-0.334	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	I
D/E	0.8424	likely_pathogenic	0.8589	pathogenic	-0.583	Destabilizing	1.0	D	0.453	neutral	D	0.524599484	None	None	I
D/F	0.9787	likely_pathogenic	0.9771	pathogenic	-0.179	Destabilizing	1.0	D	0.654	neutral	None	None	None	None	I
D/G	0.7963	likely_pathogenic	0.7745	pathogenic	-1.049	Destabilizing	1.0	D	0.721	prob.delet.	N	0.501491363	None	None	I
D/H	0.88	likely_pathogenic	0.8741	pathogenic	-0.531	Destabilizing	1.0	D	0.649	neutral	N	0.500730894	None	None	I
D/I	0.9601	likely_pathogenic	0.9571	pathogenic	0.273	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
D/K	0.9594	likely_pathogenic	0.9593	pathogenic	-0.524	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	I
D/L	0.9486	likely_pathogenic	0.9432	pathogenic	0.273	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
D/M	0.9831	likely_pathogenic	0.9813	pathogenic	0.72	Stabilizing	1.0	D	0.645	neutral	None	None	None	None	I
D/N	0.2206	likely_benign	0.2195	benign	-0.968	Destabilizing	1.0	D	0.705	prob.neutral	N	0.50580308	None	None	I
D/P	0.975	likely_pathogenic	0.9736	pathogenic	-0.023	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
D/Q	0.9371	likely_pathogenic	0.9357	pathogenic	-0.808	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
D/R	0.9447	likely_pathogenic	0.942	pathogenic	-0.343	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	I
D/S	0.4706	ambiguous	0.448	ambiguous	-1.24	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	I
D/T	0.7675	likely_pathogenic	0.7469	pathogenic	-0.94	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	I
D/V	0.901	likely_pathogenic	0.8932	pathogenic	-0.023	Destabilizing	1.0	D	0.713	prob.delet.	N	0.51158022	None	None	I
D/W	0.9949	likely_pathogenic	0.9943	pathogenic	0.042	Stabilizing	1.0	D	0.654	neutral	None	None	None	None	I
D/Y	0.861	likely_pathogenic	0.8538	pathogenic	0.058	Stabilizing	1.0	D	0.637	neutral	D	0.530951923	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.