TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16384	49375;49376;49377	chr2:178614247;178614246;178614245	chr2:179478974;179478973;179478972
N2AB	14743	44452;44453;44454	chr2:178614247;178614246;178614245	chr2:179478974;179478973;179478972
N2A	13816	41671;41672;41673	chr2:178614247;178614246;178614245	chr2:179478974;179478973;179478972
N2B	7319	22180;22181;22182	chr2:178614247;178614246;178614245	chr2:179478974;179478973;179478972
Novex-1	7444	22555;22556;22557	chr2:178614247;178614246;178614245	chr2:179478974;179478973;179478972
Novex-2	7511	22756;22757;22758	chr2:178614247;178614246;178614245	chr2:179478974;179478973;179478972
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-6
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.4143
• 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
T/P	rs1559808274	-0.322	1.0	D	0.821	0.556	0.523082183605	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.95E-06	0
T/P	rs1559808274	-0.322	1.0	D	0.821	0.556	0.523082183605	gnomAD-4.0.0	1.59351E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86146E-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
T/A	0.3348	likely_benign	0.2614	benign	-0.617	Destabilizing	0.999	D	0.545	neutral	D	0.575726709	None	None	I
T/C	0.8093	likely_pathogenic	0.7641	pathogenic	-0.337	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	I
T/D	0.9099	likely_pathogenic	0.8694	pathogenic	-0.173	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	I
T/E	0.858	likely_pathogenic	0.7884	pathogenic	-0.218	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
T/F	0.7985	likely_pathogenic	0.7467	pathogenic	-0.859	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	I
T/G	0.6716	likely_pathogenic	0.5802	pathogenic	-0.82	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	I
T/H	0.7432	likely_pathogenic	0.6842	pathogenic	-1.126	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
T/I	0.6499	likely_pathogenic	0.5412	ambiguous	-0.184	Destabilizing	1.0	D	0.831	deleterious	N	0.487702449	None	None	I
T/K	0.7044	likely_pathogenic	0.6078	pathogenic	-0.671	Destabilizing	1.0	D	0.841	deleterious	D	0.578653203	None	None	I
T/L	0.3554	ambiguous	0.2753	benign	-0.184	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	I
T/M	0.2724	likely_benign	0.2096	benign	0.144	Stabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
T/N	0.3751	ambiguous	0.3053	benign	-0.479	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
T/P	0.8926	likely_pathogenic	0.8515	pathogenic	-0.297	Destabilizing	1.0	D	0.821	deleterious	D	0.754145703	None	None	I
T/Q	0.6436	likely_pathogenic	0.5549	ambiguous	-0.721	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
T/R	0.6571	likely_pathogenic	0.5678	pathogenic	-0.354	Destabilizing	1.0	D	0.82	deleterious	N	0.509111828	None	None	I
T/S	0.2557	likely_benign	0.2163	benign	-0.714	Destabilizing	0.999	D	0.564	neutral	N	0.517744053	None	None	I
T/V	0.5011	ambiguous	0.406	ambiguous	-0.297	Destabilizing	0.999	D	0.667	neutral	None	None	None	None	I
T/W	0.9526	likely_pathogenic	0.9393	pathogenic	-0.804	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	I
T/Y	0.8296	likely_pathogenic	0.7836	pathogenic	-0.573	Destabilizing	1.0	D	0.829	deleterious	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.