TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1468	4627;4628;4629	chr2:178777782;178777781;178777780	chr2:179642509;179642508;179642507
N2AB	1468	4627;4628;4629	chr2:178777782;178777781;178777780	chr2:179642509;179642508;179642507
N2A	1468	4627;4628;4629	chr2:178777782;178777781;178777780	chr2:179642509;179642508;179642507
N2B	1422	4489;4490;4491	chr2:178777782;178777781;178777780	chr2:179642509;179642508;179642507
Novex-1	1422	4489;4490;4491	chr2:178777782;178777781;178777780	chr2:179642509;179642508;179642507
Novex-2	1422	4489;4490;4491	chr2:178777782;178777781;178777780	chr2:179642509;179642508;179642507
Novex-3	1468	4627;4628;4629	chr2:178777782;178777781;178777780	chr2:179642509;179642508;179642507

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-6
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.259
• Predicted PPI site: I

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
C/S	None	None	0.99	N	0.579	0.629	0.72213654127	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	7.32654E-05

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
C/A	0.7549	likely_pathogenic	0.7543	pathogenic	-1.712	Destabilizing	0.964	D	0.461	neutral	None	None	None	None	I
C/D	0.9904	likely_pathogenic	0.9898	pathogenic	-0.887	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	I
C/E	0.9923	likely_pathogenic	0.9918	pathogenic	-0.735	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	I
C/F	0.7414	likely_pathogenic	0.7338	pathogenic	-1.039	Destabilizing	0.997	D	0.606	neutral	N	0.507747866	None	None	I
C/G	0.673	likely_pathogenic	0.6764	pathogenic	-2.046	Highly Destabilizing	0.999	D	0.653	neutral	N	0.503918272	None	None	I
C/H	0.9624	likely_pathogenic	0.9598	pathogenic	-2.177	Highly Destabilizing	1.0	D	0.63	neutral	None	None	None	None	I
C/I	0.6707	likely_pathogenic	0.6635	pathogenic	-0.838	Destabilizing	0.971	D	0.529	neutral	None	None	None	None	I
C/K	0.9917	likely_pathogenic	0.9912	pathogenic	-1.129	Destabilizing	0.999	D	0.663	neutral	None	None	None	None	I
C/L	0.7281	likely_pathogenic	0.7242	pathogenic	-0.838	Destabilizing	0.931	D	0.494	neutral	None	None	None	None	I
C/M	0.8693	likely_pathogenic	0.8635	pathogenic	0.006	Stabilizing	0.998	D	0.577	neutral	None	None	None	None	I
C/N	0.9496	likely_pathogenic	0.9473	pathogenic	-1.301	Destabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	I
C/P	0.9972	likely_pathogenic	0.9973	pathogenic	-1.104	Destabilizing	0.999	D	0.667	neutral	None	None	None	None	I
C/Q	0.9719	likely_pathogenic	0.9708	pathogenic	-1.101	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	I
C/R	0.9487	likely_pathogenic	0.9453	pathogenic	-1.18	Destabilizing	0.999	D	0.677	prob.neutral	N	0.498798882	None	None	I
C/S	0.7468	likely_pathogenic	0.7445	pathogenic	-1.768	Destabilizing	0.99	D	0.579	neutral	N	0.495865794	None	None	I
C/T	0.7558	likely_pathogenic	0.7495	pathogenic	-1.432	Destabilizing	0.985	D	0.588	neutral	None	None	None	None	I
C/V	0.5226	ambiguous	0.513	ambiguous	-1.104	Destabilizing	0.469	N	0.369	neutral	None	None	None	None	I
C/W	0.9706	likely_pathogenic	0.969	pathogenic	-1.191	Destabilizing	1.0	D	0.583	neutral	D	0.583010668	None	None	I
C/Y	0.8801	likely_pathogenic	0.8759	pathogenic	-1.097	Destabilizing	0.999	D	0.608	neutral	N	0.508048647	None	None	I

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.