TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21943	66052;66053;66054	chr2:178582976;178582975;178582974	chr2:179447703;179447702;179447701
N2AB	20302	61129;61130;61131	chr2:178582976;178582975;178582974	chr2:179447703;179447702;179447701
N2A	19375	58348;58349;58350	chr2:178582976;178582975;178582974	chr2:179447703;179447702;179447701
N2B	12878	38857;38858;38859	chr2:178582976;178582975;178582974	chr2:179447703;179447702;179447701
Novex-1	13003	39232;39233;39234	chr2:178582976;178582975;178582974	chr2:179447703;179447702;179447701
Novex-2	13070	39433;39434;39435	chr2:178582976;178582975;178582974	chr2:179447703;179447702;179447701
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Ig-125
• Domain position: 78
• Structural Position: 164
• Q(SASA): 0.3218
• 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
G/D	None	None	1.0	D	0.803	0.789	0.496628014799	gnomAD-4.0.0	7.15228E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.27895E-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
G/A	0.8097	likely_pathogenic	0.8085	pathogenic	-0.103	Destabilizing	0.983	D	0.611	neutral	D	0.567404623	None	None	I
G/C	0.9223	likely_pathogenic	0.9234	pathogenic	-0.794	Destabilizing	1.0	D	0.778	deleterious	D	0.605993957	None	None	I
G/D	0.9592	likely_pathogenic	0.9518	pathogenic	-0.314	Destabilizing	1.0	D	0.803	deleterious	D	0.567001014	None	None	I
G/E	0.9772	likely_pathogenic	0.9767	pathogenic	-0.473	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	I
G/F	0.9881	likely_pathogenic	0.9871	pathogenic	-0.929	Destabilizing	0.999	D	0.826	deleterious	None	None	None	None	I
G/H	0.9848	likely_pathogenic	0.9827	pathogenic	-0.323	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
G/I	0.9862	likely_pathogenic	0.9849	pathogenic	-0.368	Destabilizing	0.996	D	0.781	deleterious	None	None	None	None	I
G/K	0.9842	likely_pathogenic	0.9829	pathogenic	-0.388	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	I
G/L	0.9832	likely_pathogenic	0.9817	pathogenic	-0.368	Destabilizing	0.996	D	0.791	deleterious	None	None	None	None	I
G/M	0.99	likely_pathogenic	0.9889	pathogenic	-0.407	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
G/N	0.9622	likely_pathogenic	0.9583	pathogenic	-0.146	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	I
G/P	0.999	likely_pathogenic	0.9989	pathogenic	-0.254	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	I
G/Q	0.9688	likely_pathogenic	0.9663	pathogenic	-0.401	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	I
G/R	0.9554	likely_pathogenic	0.9494	pathogenic	-0.062	Destabilizing	0.999	D	0.818	deleterious	D	0.604984936	None	None	I
G/S	0.7165	likely_pathogenic	0.7167	pathogenic	-0.277	Destabilizing	0.999	D	0.787	deleterious	D	0.560530764	None	None	I
G/T	0.9506	likely_pathogenic	0.9476	pathogenic	-0.37	Destabilizing	0.998	D	0.795	deleterious	None	None	None	None	I
G/V	0.9711	likely_pathogenic	0.9696	pathogenic	-0.254	Destabilizing	0.652	D	0.584	neutral	D	0.62160971	None	None	I
G/W	0.9876	likely_pathogenic	0.9849	pathogenic	-1.056	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
G/Y	0.985	likely_pathogenic	0.9829	pathogenic	-0.707	Destabilizing	1.0	D	0.828	deleterious	None	None	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.