TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10123	30592;30593;30594	chr2:178702520;178702519;178702518	chr2:179567247;179567246;179567245
N2AB	9806	29641;29642;29643	chr2:178702520;178702519;178702518	chr2:179567247;179567246;179567245
N2A	8879	26860;26861;26862	chr2:178702520;178702519;178702518	chr2:179567247;179567246;179567245
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-86
• Domain position: 46
• Structural Position: 121
• Q(SASA): 0.1469
• 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
Y/C	None	None	1.0	None	0.839	0.757	0.77875509527	gnomAD-4.0.0	1.59086E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-05	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
Y/A	0.9967	likely_pathogenic	0.9975	pathogenic	-2.496	Highly Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
Y/C	0.9523	likely_pathogenic	0.9697	pathogenic	-1.55	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
Y/D	0.9951	likely_pathogenic	0.9975	pathogenic	-2.415	Highly Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
Y/E	0.9984	likely_pathogenic	0.999	pathogenic	-2.198	Highly Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
Y/F	0.4768	ambiguous	0.5248	ambiguous	-0.748	Destabilizing	0.999	D	0.507	neutral	None	None	None	None	N
Y/G	0.9901	likely_pathogenic	0.9924	pathogenic	-2.933	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
Y/H	0.9559	likely_pathogenic	0.9793	pathogenic	-1.631	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
Y/I	0.98	likely_pathogenic	0.9842	pathogenic	-1.075	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
Y/K	0.9982	likely_pathogenic	0.9988	pathogenic	-1.689	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
Y/L	0.9672	likely_pathogenic	0.9706	pathogenic	-1.075	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
Y/M	0.991	likely_pathogenic	0.9928	pathogenic	-0.976	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
Y/N	0.9672	likely_pathogenic	0.9826	pathogenic	-2.445	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
Y/P	0.9988	likely_pathogenic	0.9994	pathogenic	-1.559	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
Y/Q	0.9981	likely_pathogenic	0.9987	pathogenic	-2.136	Highly Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
Y/R	0.9946	likely_pathogenic	0.9959	pathogenic	-1.627	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
Y/S	0.9914	likely_pathogenic	0.9942	pathogenic	-2.92	Highly Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
Y/T	0.9948	likely_pathogenic	0.9967	pathogenic	-2.572	Highly Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
Y/V	0.9614	likely_pathogenic	0.9685	pathogenic	-1.559	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
Y/W	0.8723	likely_pathogenic	0.9135	pathogenic	-0.082	Destabilizing	1.0	D	0.707	prob.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.