TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9564	28915;28916;28917	chr2:178709629;178709628;178709627	chr2:179574356;179574355;179574354
N2AB	9247	27964;27965;27966	chr2:178709629;178709628;178709627	chr2:179574356;179574355;179574354
N2A	8320	25183;25184;25185	chr2:178709629;178709628;178709627	chr2:179574356;179574355;179574354
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-81
• Domain position: 72
• Structural Position: 154
• Q(SASA): 0.1433
• 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	rs2076368966	None	1.0	None	0.87	0.873	0.885172764854	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.06782E-04	0
Y/C	rs2076368966	None	1.0	None	0.87	0.873	0.885172764854	gnomAD-4.0.0	6.5684E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.06782E-04	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	0.9941	likely_pathogenic	0.9959	pathogenic	-1.892	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
Y/C	0.8894	likely_pathogenic	0.94	pathogenic	-1.302	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
Y/D	0.9981	likely_pathogenic	0.9986	pathogenic	-2.348	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
Y/E	0.9988	likely_pathogenic	0.9992	pathogenic	-2.098	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
Y/F	0.1672	likely_benign	0.1772	benign	-0.55	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
Y/G	0.9923	likely_pathogenic	0.994	pathogenic	-2.342	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
Y/H	0.9503	likely_pathogenic	0.9685	pathogenic	-1.8	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
Y/I	0.8816	likely_pathogenic	0.9274	pathogenic	-0.414	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
Y/K	0.9988	likely_pathogenic	0.9993	pathogenic	-1.405	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/L	0.7666	likely_pathogenic	0.8054	pathogenic	-0.414	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
Y/M	0.9688	likely_pathogenic	0.9794	pathogenic	-0.569	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
Y/N	0.9848	likely_pathogenic	0.9906	pathogenic	-2.267	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
Y/P	0.9984	likely_pathogenic	0.9987	pathogenic	-0.92	Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
Y/Q	0.9977	likely_pathogenic	0.9986	pathogenic	-1.806	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
Y/R	0.9936	likely_pathogenic	0.9958	pathogenic	-1.778	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
Y/S	0.987	likely_pathogenic	0.9917	pathogenic	-2.625	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
Y/T	0.9944	likely_pathogenic	0.9967	pathogenic	-2.225	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
Y/V	0.8541	likely_pathogenic	0.8986	pathogenic	-0.92	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
Y/W	0.7911	likely_pathogenic	0.8085	pathogenic	0.062	Stabilizing	1.0	D	0.786	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.