TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20678	62257;62258;62259	chr2:178589693;178589692;178589691	chr2:179454420;179454419;179454418
N2AB	19037	57334;57335;57336	chr2:178589693;178589692;178589691	chr2:179454420;179454419;179454418
N2A	18110	54553;54554;54555	chr2:178589693;178589692;178589691	chr2:179454420;179454419;179454418
N2B	11613	35062;35063;35064	chr2:178589693;178589692;178589691	chr2:179454420;179454419;179454418
Novex-1	11738	35437;35438;35439	chr2:178589693;178589692;178589691	chr2:179454420;179454419;179454418
Novex-2	11805	35638;35639;35640	chr2:178589693;178589692;178589691	chr2:179454420;179454419;179454418
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-38
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.1801
• Predicted PPI site: N

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
A/V	None	None	0.852	N	0.454	0.204	0.371344866733	gnomAD-4.0.0	1.5918E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85938E-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
A/C	0.626	likely_pathogenic	0.5969	pathogenic	-0.501	Destabilizing	0.999	D	0.467	neutral	None	None	None	None	N
A/D	0.8007	likely_pathogenic	0.7128	pathogenic	-1.117	Destabilizing	0.991	D	0.497	neutral	None	None	None	None	N
A/E	0.6609	likely_pathogenic	0.5651	pathogenic	-1.159	Destabilizing	0.988	D	0.451	neutral	N	0.422779052	None	None	N
A/F	0.647	likely_pathogenic	0.5557	ambiguous	-0.89	Destabilizing	0.982	D	0.555	neutral	None	None	None	None	N
A/G	0.3261	likely_benign	0.307	benign	-0.964	Destabilizing	0.035	N	0.141	neutral	N	0.440039448	None	None	N
A/H	0.7631	likely_pathogenic	0.7284	pathogenic	-1.146	Destabilizing	0.999	D	0.516	neutral	None	None	None	None	N
A/I	0.5178	ambiguous	0.4225	ambiguous	-0.282	Destabilizing	0.884	D	0.426	neutral	None	None	None	None	N
A/K	0.8739	likely_pathogenic	0.8235	pathogenic	-1.118	Destabilizing	0.969	D	0.449	neutral	None	None	None	None	N
A/L	0.3911	ambiguous	0.3239	benign	-0.282	Destabilizing	0.046	N	0.315	neutral	None	None	None	None	N
A/M	0.4321	ambiguous	0.3834	ambiguous	-0.185	Destabilizing	0.982	D	0.49	neutral	None	None	None	None	N
A/N	0.6533	likely_pathogenic	0.5629	ambiguous	-0.732	Destabilizing	0.991	D	0.497	neutral	None	None	None	None	N
A/P	0.9289	likely_pathogenic	0.8952	pathogenic	-0.395	Destabilizing	0.996	D	0.479	neutral	N	0.458798567	None	None	N
A/Q	0.5962	likely_pathogenic	0.5545	ambiguous	-0.905	Destabilizing	0.997	D	0.506	neutral	None	None	None	None	N
A/R	0.7937	likely_pathogenic	0.7429	pathogenic	-0.726	Destabilizing	0.991	D	0.484	neutral	None	None	None	None	N
A/S	0.1438	likely_benign	0.1274	benign	-0.987	Destabilizing	0.704	D	0.479	neutral	N	0.389991843	None	None	N
A/T	0.1609	likely_benign	0.1351	benign	-0.947	Destabilizing	0.061	N	0.11	neutral	N	0.347491859	None	None	N
A/V	0.266	likely_benign	0.2271	benign	-0.395	Destabilizing	0.852	D	0.454	neutral	N	0.380721785	None	None	N
A/W	0.9163	likely_pathogenic	0.8801	pathogenic	-1.249	Destabilizing	0.999	D	0.605	neutral	None	None	None	None	N
A/Y	0.7994	likely_pathogenic	0.7308	pathogenic	-0.848	Destabilizing	0.997	D	0.542	neutral	None	None	None	None	N

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.