TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19791	59596;59597;59598	chr2:178592634;178592633;178592632	chr2:179457361;179457360;179457359
N2AB	18150	54673;54674;54675	chr2:178592634;178592633;178592632	chr2:179457361;179457360;179457359
N2A	17223	51892;51893;51894	chr2:178592634;178592633;178592632	chr2:179457361;179457360;179457359
N2B	10726	32401;32402;32403	chr2:178592634;178592633;178592632	chr2:179457361;179457360;179457359
Novex-1	10851	32776;32777;32778	chr2:178592634;178592633;178592632	chr2:179457361;179457360;179457359
Novex-2	10918	32977;32978;32979	chr2:178592634;178592633;178592632	chr2:179457361;179457360;179457359
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: Ig-119
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.619
• 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/I	rs2050467493	None	0.988	N	0.475	0.344	0.558850992237	gnomAD-4.0.0	1.36889E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.7993E-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	0.3648	ambiguous	0.4419	ambiguous	-0.501	Destabilizing	0.17	N	0.256	neutral	None	None	None	None	N
N/C	0.5298	ambiguous	0.6108	pathogenic	0.275	Stabilizing	0.999	D	0.453	neutral	None	None	None	None	N
N/D	0.2918	likely_benign	0.3957	ambiguous	0.071	Stabilizing	0.959	D	0.427	neutral	N	0.430542891	None	None	N
N/E	0.6764	likely_pathogenic	0.7836	pathogenic	0.077	Stabilizing	0.969	D	0.383	neutral	None	None	None	None	N
N/F	0.7953	likely_pathogenic	0.8271	pathogenic	-0.699	Destabilizing	0.997	D	0.462	neutral	None	None	None	None	N
N/G	0.3669	ambiguous	0.4369	ambiguous	-0.734	Destabilizing	0.007	N	0.141	neutral	None	None	None	None	N
N/H	0.2015	likely_benign	0.2751	benign	-0.668	Destabilizing	0.996	D	0.467	neutral	N	0.497959962	None	None	N
N/I	0.5745	likely_pathogenic	0.6688	pathogenic	0.039	Stabilizing	0.988	D	0.475	neutral	N	0.498306678	None	None	N
N/K	0.6605	likely_pathogenic	0.7997	pathogenic	-0.001	Destabilizing	0.959	D	0.389	neutral	N	0.413245209	None	None	N
N/L	0.4862	ambiguous	0.5701	pathogenic	0.039	Stabilizing	0.939	D	0.431	neutral	None	None	None	None	N
N/M	0.6097	likely_pathogenic	0.6938	pathogenic	0.361	Stabilizing	0.999	D	0.456	neutral	None	None	None	None	N
N/P	0.7384	likely_pathogenic	0.8561	pathogenic	-0.113	Destabilizing	0.997	D	0.457	neutral	None	None	None	None	N
N/Q	0.5927	likely_pathogenic	0.6923	pathogenic	-0.471	Destabilizing	0.997	D	0.45	neutral	None	None	None	None	N
N/R	0.6499	likely_pathogenic	0.7758	pathogenic	0.016	Stabilizing	0.991	D	0.42	neutral	None	None	None	None	N
N/S	0.0975	likely_benign	0.1183	benign	-0.344	Destabilizing	0.704	D	0.481	neutral	N	0.40091063	None	None	N
N/T	0.2265	likely_benign	0.2956	benign	-0.17	Destabilizing	0.92	D	0.397	neutral	N	0.467637055	None	None	N
N/V	0.4723	ambiguous	0.5637	ambiguous	-0.113	Destabilizing	0.939	D	0.423	neutral	None	None	None	None	N
N/W	0.9021	likely_pathogenic	0.9357	pathogenic	-0.621	Destabilizing	0.999	D	0.563	neutral	None	None	None	None	N
N/Y	0.3967	ambiguous	0.4697	ambiguous	-0.375	Destabilizing	0.996	D	0.464	neutral	N	0.498480037	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.