TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18119	54580;54581;54582	chr2:178604734;178604733;178604732	chr2:179469461;179469460;179469459
N2AB	16478	49657;49658;49659	chr2:178604734;178604733;178604732	chr2:179469461;179469460;179469459
N2A	15551	46876;46877;46878	chr2:178604734;178604733;178604732	chr2:179469461;179469460;179469459
N2B	9054	27385;27386;27387	chr2:178604734;178604733;178604732	chr2:179469461;179469460;179469459
Novex-1	9179	27760;27761;27762	chr2:178604734;178604733;178604732	chr2:179469461;179469460;179469459
Novex-2	9246	27961;27962;27963	chr2:178604734;178604733;178604732	chr2:179469461;179469460;179469459
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-19
• Domain position: 55
• Structural Position: 70
• Q(SASA): 0.6669
• 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
N/K	None	None	0.026	N	0.154	0.133	0.112648838833	gnomAD-4.0.0	3.601E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.93753E-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
N/A	0.1406	likely_benign	0.1558	benign	-0.562	Destabilizing	0.919	D	0.522	neutral	None	None	None	None	N
N/C	0.2382	likely_benign	0.2424	benign	0.349	Stabilizing	0.999	D	0.675	neutral	None	None	None	None	N
N/D	0.1314	likely_benign	0.1311	benign	-0.431	Destabilizing	0.896	D	0.469	neutral	N	0.395075162	None	None	N
N/E	0.3107	likely_benign	0.3412	ambiguous	-0.425	Destabilizing	0.851	D	0.458	neutral	None	None	None	None	N
N/F	0.5608	ambiguous	0.5992	pathogenic	-0.664	Destabilizing	0.996	D	0.646	neutral	None	None	None	None	N
N/G	0.1732	likely_benign	0.2118	benign	-0.814	Destabilizing	0.919	D	0.476	neutral	None	None	None	None	N
N/H	0.1218	likely_benign	0.1337	benign	-0.826	Destabilizing	0.995	D	0.486	neutral	N	0.459510643	None	None	N
N/I	0.2876	likely_benign	0.2984	benign	0.037	Stabilizing	0.968	D	0.631	neutral	N	0.467684622	None	None	N
N/K	0.2104	likely_benign	0.2433	benign	-0.177	Destabilizing	0.026	N	0.154	neutral	N	0.391920214	None	None	N
N/L	0.2455	likely_benign	0.2623	benign	0.037	Stabilizing	0.919	D	0.512	neutral	None	None	None	None	N
N/M	0.3392	likely_benign	0.3706	ambiguous	0.614	Stabilizing	0.999	D	0.619	neutral	None	None	None	None	N
N/P	0.3719	ambiguous	0.4357	ambiguous	-0.134	Destabilizing	0.988	D	0.619	neutral	None	None	None	None	N
N/Q	0.2517	likely_benign	0.2924	benign	-0.699	Destabilizing	0.976	D	0.468	neutral	None	None	None	None	N
N/R	0.2429	likely_benign	0.27	benign	-0.104	Destabilizing	0.851	D	0.455	neutral	None	None	None	None	N
N/S	0.0687	likely_benign	0.0721	benign	-0.461	Destabilizing	0.64	D	0.507	neutral	N	0.394979162	None	None	N
N/T	0.1058	likely_benign	0.118	benign	-0.3	Destabilizing	0.103	N	0.273	neutral	N	0.359269078	None	None	N
N/V	0.2261	likely_benign	0.2361	benign	-0.134	Destabilizing	0.976	D	0.517	neutral	None	None	None	None	N
N/W	0.7599	likely_pathogenic	0.7671	pathogenic	-0.544	Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	N
N/Y	0.2131	likely_benign	0.2333	benign	-0.329	Destabilizing	0.995	D	0.621	neutral	N	0.455200901	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.