TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24478	73657;73658;73659	chr2:178572700;178572699;178572698	chr2:179437427;179437426;179437425
N2AB	22837	68734;68735;68736	chr2:178572700;178572699;178572698	chr2:179437427;179437426;179437425
N2A	21910	65953;65954;65955	chr2:178572700;178572699;178572698	chr2:179437427;179437426;179437425
N2B	15413	46462;46463;46464	chr2:178572700;178572699;178572698	chr2:179437427;179437426;179437425
Novex-1	15538	46837;46838;46839	chr2:178572700;178572699;178572698	chr2:179437427;179437426;179437425
Novex-2	15605	47038;47039;47040	chr2:178572700;178572699;178572698	chr2:179437427;179437426;179437425
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-132
• Domain position: 48
• Structural Position: 130
• Q(SASA): 0.2288
• 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
T/I	None	None	0.976	N	0.517	0.491	0.674603152142	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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
T/A	0.3128	likely_benign	0.3438	ambiguous	-0.551	Destabilizing	0.958	D	0.379	neutral	N	0.499722115	None	None	N
T/C	0.8374	likely_pathogenic	0.8571	pathogenic	-0.287	Destabilizing	1.0	D	0.613	neutral	None	None	None	None	N
T/D	0.7459	likely_pathogenic	0.7623	pathogenic	0.726	Stabilizing	0.998	D	0.588	neutral	None	None	None	None	N
T/E	0.8643	likely_pathogenic	0.888	pathogenic	0.664	Stabilizing	0.995	D	0.549	neutral	None	None	None	None	N
T/F	0.8435	likely_pathogenic	0.8747	pathogenic	-1.048	Destabilizing	0.991	D	0.651	neutral	None	None	None	None	N
T/G	0.4722	ambiguous	0.5358	ambiguous	-0.678	Destabilizing	0.995	D	0.543	neutral	None	None	None	None	N
T/H	0.695	likely_pathogenic	0.7336	pathogenic	-0.932	Destabilizing	1.0	D	0.656	neutral	None	None	None	None	N
T/I	0.8095	likely_pathogenic	0.8429	pathogenic	-0.333	Destabilizing	0.976	D	0.517	neutral	N	0.494241613	None	None	N
T/K	0.7656	likely_pathogenic	0.8007	pathogenic	-0.159	Destabilizing	0.988	D	0.537	neutral	N	0.492667769	None	None	N
T/L	0.4477	ambiguous	0.5044	ambiguous	-0.333	Destabilizing	0.839	D	0.418	neutral	None	None	None	None	N
T/M	0.3876	ambiguous	0.444	ambiguous	-0.142	Destabilizing	0.862	D	0.353	neutral	None	None	None	None	N
T/N	0.3272	likely_benign	0.3384	benign	0.001	Stabilizing	0.995	D	0.569	neutral	None	None	None	None	N
T/P	0.7232	likely_pathogenic	0.7479	pathogenic	-0.378	Destabilizing	0.998	D	0.575	neutral	N	0.498356216	None	None	N
T/Q	0.7075	likely_pathogenic	0.7578	pathogenic	-0.176	Destabilizing	0.995	D	0.602	neutral	None	None	None	None	N
T/R	0.7315	likely_pathogenic	0.7716	pathogenic	0.016	Stabilizing	0.994	D	0.576	neutral	N	0.496835279	None	None	N
T/S	0.1899	likely_benign	0.2114	benign	-0.324	Destabilizing	0.958	D	0.376	neutral	N	0.502312563	None	None	N
T/V	0.6421	likely_pathogenic	0.6802	pathogenic	-0.378	Destabilizing	0.938	D	0.387	neutral	None	None	None	None	N
T/W	0.9682	likely_pathogenic	0.9765	pathogenic	-1.007	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
T/Y	0.8643	likely_pathogenic	0.8868	pathogenic	-0.726	Destabilizing	0.995	D	0.669	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.