TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23720	71383;71384;71385	chr2:178574974;178574973;178574972	chr2:179439701;179439700;179439699
N2AB	22079	66460;66461;66462	chr2:178574974;178574973;178574972	chr2:179439701;179439700;179439699
N2A	21152	63679;63680;63681	chr2:178574974;178574973;178574972	chr2:179439701;179439700;179439699
N2B	14655	44188;44189;44190	chr2:178574974;178574973;178574972	chr2:179439701;179439700;179439699
Novex-1	14780	44563;44564;44565	chr2:178574974;178574973;178574972	chr2:179439701;179439700;179439699
Novex-2	14847	44764;44765;44766	chr2:178574974;178574973;178574972	chr2:179439701;179439700;179439699
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-130
• Domain position: 84
• Structural Position: 173
• Q(SASA): 0.4797
• 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	0.997	D	0.776	0.468	0.61789491966	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05
T/S	rs1709538154	None	0.362	N	0.363	0.14	0.340032825777	gnomAD-4.0.0	1.59251E-06	None	None	None	None	N	None	5.65803E-05	0	None	0	0	None	0	0	0	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	0.1045	likely_benign	0.1058	benign	-0.791	Destabilizing	0.898	D	0.524	neutral	D	0.525978856	None	None	N
T/C	0.3628	ambiguous	0.3799	ambiguous	-0.548	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
T/D	0.3741	ambiguous	0.3823	ambiguous	-0.33	Destabilizing	0.995	D	0.721	prob.delet.	None	None	None	None	N
T/E	0.3084	likely_benign	0.3145	benign	-0.222	Destabilizing	0.995	D	0.718	prob.delet.	None	None	None	None	N
T/F	0.227	likely_benign	0.228	benign	-0.538	Destabilizing	0.999	D	0.778	deleterious	None	None	None	None	N
T/G	0.3185	likely_benign	0.3202	benign	-1.143	Destabilizing	0.966	D	0.679	prob.neutral	None	None	None	None	N
T/H	0.1892	likely_benign	0.2005	benign	-1.318	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
T/I	0.1446	likely_benign	0.1447	benign	0.089	Stabilizing	0.997	D	0.776	deleterious	D	0.533406261	None	None	N
T/K	0.2092	likely_benign	0.2185	benign	-0.53	Destabilizing	0.995	D	0.721	prob.delet.	None	None	None	None	N
T/L	0.1009	likely_benign	0.102	benign	0.089	Stabilizing	0.983	D	0.669	neutral	None	None	None	None	N
T/M	0.0962	likely_benign	0.0941	benign	0.02	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
T/N	0.1073	likely_benign	0.111	benign	-0.802	Destabilizing	0.993	D	0.682	prob.neutral	N	0.501389843	None	None	N
T/P	0.4852	ambiguous	0.4507	ambiguous	-0.171	Destabilizing	0.997	D	0.771	deleterious	N	0.502724309	None	None	N
T/Q	0.2075	likely_benign	0.2213	benign	-0.725	Destabilizing	0.998	D	0.763	deleterious	None	None	None	None	N
T/R	0.1873	likely_benign	0.1885	benign	-0.574	Destabilizing	0.995	D	0.767	deleterious	None	None	None	None	N
T/S	0.1101	likely_benign	0.1116	benign	-1.088	Destabilizing	0.362	N	0.363	neutral	N	0.495519876	None	None	N
T/V	0.1217	likely_benign	0.1246	benign	-0.171	Destabilizing	0.983	D	0.604	neutral	None	None	None	None	N
T/W	0.5708	likely_pathogenic	0.5548	ambiguous	-0.586	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
T/Y	0.2138	likely_benign	0.2228	benign	-0.269	Destabilizing	0.999	D	0.771	deleterious	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.