TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7125	21598;21599;21600	chr2:178723886;178723885;178723884	chr2:179588613;179588612;179588611
N2AB	6808	20647;20648;20649	chr2:178723886;178723885;178723884	chr2:179588613;179588612;179588611
N2A	5881	17866;17867;17868	chr2:178723886;178723885;178723884	chr2:179588613;179588612;179588611
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-55
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.2421
• 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/N	None	None	0.999	N	0.596	0.371	0.423954403188	gnomAD-4.0.0	1.59427E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86475E-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	0.191	likely_benign	0.1801	benign	-0.704	Destabilizing	0.98	D	0.682	prob.neutral	N	0.443378902	None	None	I
D/C	0.8165	likely_pathogenic	0.7784	pathogenic	-0.227	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
D/E	0.3058	likely_benign	0.2891	benign	-0.63	Destabilizing	0.997	D	0.511	neutral	N	0.491858075	None	None	I
D/F	0.832	likely_pathogenic	0.7959	pathogenic	-0.302	Destabilizing	0.998	D	0.823	deleterious	None	None	None	None	I
D/G	0.2494	likely_benign	0.2297	benign	-1.047	Destabilizing	0.997	D	0.645	neutral	N	0.514307651	None	None	I
D/H	0.4927	ambiguous	0.4263	ambiguous	-0.54	Destabilizing	1.0	D	0.663	neutral	N	0.520891016	None	None	I
D/I	0.6761	likely_pathogenic	0.6349	pathogenic	0.202	Stabilizing	0.971	D	0.746	deleterious	None	None	None	None	I
D/K	0.5541	ambiguous	0.5004	ambiguous	-0.193	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	I
D/L	0.6704	likely_pathogenic	0.6349	pathogenic	0.202	Stabilizing	0.971	D	0.743	deleterious	None	None	None	None	I
D/M	0.827	likely_pathogenic	0.8039	pathogenic	0.634	Stabilizing	0.999	D	0.81	deleterious	None	None	None	None	I
D/N	0.1497	likely_benign	0.1319	benign	-0.665	Destabilizing	0.999	D	0.596	neutral	N	0.496999863	None	None	I
D/P	0.9796	likely_pathogenic	0.9729	pathogenic	-0.076	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	I
D/Q	0.5303	ambiguous	0.4788	ambiguous	-0.561	Destabilizing	0.999	D	0.577	neutral	None	None	None	None	I
D/R	0.5662	likely_pathogenic	0.5062	ambiguous	-0.042	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	I
D/S	0.1333	likely_benign	0.1195	benign	-0.934	Destabilizing	0.993	D	0.579	neutral	None	None	None	None	I
D/T	0.3829	ambiguous	0.3491	ambiguous	-0.646	Destabilizing	0.985	D	0.647	neutral	None	None	None	None	I
D/V	0.4097	ambiguous	0.372	ambiguous	-0.076	Destabilizing	0.219	N	0.515	neutral	N	0.493018289	None	None	I
D/W	0.9694	likely_pathogenic	0.9586	pathogenic	-0.056	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	I
D/Y	0.4987	ambiguous	0.4307	ambiguous	-0.02	Destabilizing	0.999	D	0.821	deleterious	D	0.532665395	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.