TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34422	103489;103490;103491	chr2:178533351;178533350;178533349	chr2:179398078;179398077;179398076
N2AB	32781	98566;98567;98568	chr2:178533351;178533350;178533349	chr2:179398078;179398077;179398076
N2A	31854	95785;95786;95787	chr2:178533351;178533350;178533349	chr2:179398078;179398077;179398076
N2B	25357	76294;76295;76296	chr2:178533351;178533350;178533349	chr2:179398078;179398077;179398076
Novex-1	25482	76669;76670;76671	chr2:178533351;178533350;178533349	chr2:179398078;179398077;179398076
Novex-2	25549	76870;76871;76872	chr2:178533351;178533350;178533349	chr2:179398078;179398077;179398076
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-162
• Domain position: 60
• Structural Position: 139
• Q(SASA): 0.3995
• 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
H/Q	None	None	0.989	N	0.531	0.354	0.396645960531	gnomAD-4.0.0	6.84291E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99413E-07	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
H/A	0.8829	likely_pathogenic	0.8564	pathogenic	-1.306	Destabilizing	0.915	D	0.529	neutral	None	None	None	None	N
H/C	0.4565	ambiguous	0.4517	ambiguous	-0.571	Destabilizing	0.998	D	0.621	neutral	None	None	None	None	N
H/D	0.8836	likely_pathogenic	0.8558	pathogenic	-1.017	Destabilizing	0.989	D	0.531	neutral	N	0.47529932	None	None	N
H/E	0.8427	likely_pathogenic	0.7939	pathogenic	-0.885	Destabilizing	0.971	D	0.497	neutral	None	None	None	None	N
H/F	0.5231	ambiguous	0.4795	ambiguous	0.153	Stabilizing	0.016	N	0.364	neutral	None	None	None	None	N
H/G	0.9437	likely_pathogenic	0.9295	pathogenic	-1.684	Destabilizing	0.915	D	0.534	neutral	None	None	None	None	N
H/I	0.6264	likely_pathogenic	0.5925	pathogenic	-0.229	Destabilizing	0.067	N	0.513	neutral	None	None	None	None	N
H/K	0.7767	likely_pathogenic	0.7364	pathogenic	-1.076	Destabilizing	0.991	D	0.527	neutral	None	None	None	None	N
H/L	0.304	likely_benign	0.2962	benign	-0.229	Destabilizing	0.454	N	0.527	neutral	N	0.431604471	None	None	N
H/M	0.7955	likely_pathogenic	0.7686	pathogenic	-0.416	Destabilizing	0.974	D	0.577	neutral	None	None	None	None	N
H/N	0.4712	ambiguous	0.4201	ambiguous	-1.229	Destabilizing	0.961	D	0.532	neutral	N	0.461562018	None	None	N
H/P	0.9635	likely_pathogenic	0.9609	pathogenic	-0.572	Destabilizing	0.989	D	0.575	neutral	N	0.486110857	None	None	N
H/Q	0.6568	likely_pathogenic	0.5847	pathogenic	-0.9	Destabilizing	0.989	D	0.531	neutral	N	0.431759186	None	None	N
H/R	0.4668	ambiguous	0.4104	ambiguous	-1.445	Destabilizing	0.989	D	0.519	neutral	N	0.416941663	None	None	N
H/S	0.7925	likely_pathogenic	0.7612	pathogenic	-1.336	Destabilizing	0.915	D	0.489	neutral	None	None	None	None	N
H/T	0.8121	likely_pathogenic	0.7839	pathogenic	-1.104	Destabilizing	0.974	D	0.565	neutral	None	None	None	None	N
H/V	0.6051	likely_pathogenic	0.5726	pathogenic	-0.572	Destabilizing	0.728	D	0.539	neutral	None	None	None	None	N
H/W	0.5775	likely_pathogenic	0.582	pathogenic	0.493	Stabilizing	0.998	D	0.588	neutral	None	None	None	None	N
H/Y	0.1815	likely_benign	0.1675	benign	0.515	Stabilizing	0.669	D	0.505	neutral	N	0.483284085	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.