TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30304	91135;91136;91137	chr2:178551990;178551989;178551988	chr2:179416717;179416716;179416715
N2AB	28663	86212;86213;86214	chr2:178551990;178551989;178551988	chr2:179416717;179416716;179416715
N2A	27736	83431;83432;83433	chr2:178551990;178551989;178551988	chr2:179416717;179416716;179416715
N2B	21239	63940;63941;63942	chr2:178551990;178551989;178551988	chr2:179416717;179416716;179416715
Novex-1	21364	64315;64316;64317	chr2:178551990;178551989;178551988	chr2:179416717;179416716;179416715
Novex-2	21431	64516;64517;64518	chr2:178551990;178551989;178551988	chr2:179416717;179416716;179416715
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-108
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.7356
• 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
R/G	None	None	0.98	N	0.587	0.299	0.534668972696	gnomAD-4.0.0	3.19291E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.87181E-06	1.43468E-05	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
R/A	0.8067	likely_pathogenic	0.7944	pathogenic	-0.047	Destabilizing	0.931	D	0.51	neutral	None	None	None	None	I
R/C	0.4691	ambiguous	0.4974	ambiguous	-0.224	Destabilizing	1.0	D	0.608	neutral	None	None	None	None	I
R/D	0.9526	likely_pathogenic	0.9506	pathogenic	-0.12	Destabilizing	0.996	D	0.533	neutral	None	None	None	None	I
R/E	0.8278	likely_pathogenic	0.8171	pathogenic	-0.049	Destabilizing	0.97	D	0.456	neutral	None	None	None	None	I
R/F	0.9079	likely_pathogenic	0.9048	pathogenic	-0.298	Destabilizing	0.999	D	0.575	neutral	None	None	None	None	I
R/G	0.7813	likely_pathogenic	0.7597	pathogenic	-0.237	Destabilizing	0.98	D	0.587	neutral	N	0.480791944	None	None	I
R/H	0.3128	likely_benign	0.3189	benign	-0.879	Destabilizing	0.999	D	0.449	neutral	None	None	None	None	I
R/I	0.6039	likely_pathogenic	0.5503	ambiguous	0.417	Stabilizing	0.998	D	0.586	neutral	N	0.516614719	None	None	I
R/K	0.219	likely_benign	0.184	benign	-0.112	Destabilizing	0.122	N	0.19	neutral	N	0.477613614	None	None	I
R/L	0.6258	likely_pathogenic	0.5954	pathogenic	0.417	Stabilizing	0.985	D	0.587	neutral	None	None	None	None	I
R/M	0.7159	likely_pathogenic	0.6613	pathogenic	-0.069	Destabilizing	1.0	D	0.528	neutral	None	None	None	None	I
R/N	0.9073	likely_pathogenic	0.8948	pathogenic	0.033	Stabilizing	0.985	D	0.497	neutral	None	None	None	None	I
R/P	0.8361	likely_pathogenic	0.8465	pathogenic	0.283	Stabilizing	0.999	D	0.575	neutral	None	None	None	None	I
R/Q	0.2747	likely_benign	0.2793	benign	-0.012	Destabilizing	0.97	D	0.521	neutral	None	None	None	None	I
R/S	0.8765	likely_pathogenic	0.8759	pathogenic	-0.268	Destabilizing	0.961	D	0.577	neutral	N	0.505434934	None	None	I
R/T	0.7207	likely_pathogenic	0.6628	pathogenic	-0.059	Destabilizing	0.98	D	0.593	neutral	N	0.468517948	None	None	I
R/V	0.7195	likely_pathogenic	0.6961	pathogenic	0.283	Stabilizing	0.996	D	0.549	neutral	None	None	None	None	I
R/W	0.5746	likely_pathogenic	0.5723	pathogenic	-0.401	Destabilizing	1.0	D	0.63	neutral	None	None	None	None	I
R/Y	0.782	likely_pathogenic	0.7919	pathogenic	0.017	Stabilizing	0.999	D	0.575	neutral	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.