TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5565	16918;16919;16920	chr2:178732276;178732275;178732274	chr2:179597003;179597002;179597001
N2AB	5248	15967;15968;15969	chr2:178732276;178732275;178732274	chr2:179597003;179597002;179597001
N2A	4321	13186;13187;13188	chr2:178732276;178732275;178732274	chr2:179597003;179597002;179597001
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: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-39
• Domain position: 23
• Structural Position: 33
• Q(SASA): 0.1098
• Site annotation: disulfide
• 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
C/S	rs1228967454	-2.29	0.961	D	0.768	0.505	0.752617791773	gnomAD-2.1.1	4.03E-06	None	None	disulfide	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
C/S	rs1228967454	-2.29	0.961	D	0.768	0.505	0.752617791773	gnomAD-4.0.0	1.59171E-06	None	None	disulfide	None	N	None	0	0	None	0	0	None	0	0	2.8591E-06	0	0
C/Y	None	None	0.999	D	0.829	0.491	0.814251235553	gnomAD-4.0.0	1.20032E-06	None	None	disulfide	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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
C/A	0.6714	likely_pathogenic	0.7079	pathogenic	-1.778	Destabilizing	0.469	N	0.427	neutral	None	None	disulfide	None	N
C/D	0.9962	likely_pathogenic	0.9963	pathogenic	-1.619	Destabilizing	0.998	D	0.862	deleterious	None	None	disulfide	None	N
C/E	0.9976	likely_pathogenic	0.9975	pathogenic	-1.388	Destabilizing	0.998	D	0.864	deleterious	None	None	disulfide	None	N
C/F	0.7291	likely_pathogenic	0.7172	pathogenic	-1.068	Destabilizing	0.999	D	0.825	deleterious	D	0.565206012	disulfide	None	N
C/G	0.5064	ambiguous	0.5336	ambiguous	-2.148	Highly Destabilizing	0.98	D	0.85	deleterious	D	0.553849707	disulfide	None	N
C/H	0.989	likely_pathogenic	0.9894	pathogenic	-2.317	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	disulfide	None	N
C/I	0.8131	likely_pathogenic	0.8024	pathogenic	-0.775	Destabilizing	0.998	D	0.803	deleterious	None	None	disulfide	None	N
C/K	0.9979	likely_pathogenic	0.998	pathogenic	-1.388	Destabilizing	0.998	D	0.861	deleterious	None	None	disulfide	None	N
C/L	0.7731	likely_pathogenic	0.7741	pathogenic	-0.775	Destabilizing	0.985	D	0.752	deleterious	None	None	disulfide	None	N
C/M	0.9035	likely_pathogenic	0.9019	pathogenic	0.267	Stabilizing	1.0	D	0.765	deleterious	None	None	disulfide	None	N
C/N	0.9818	likely_pathogenic	0.9828	pathogenic	-1.965	Destabilizing	0.999	D	0.861	deleterious	None	None	disulfide	None	N
C/P	0.996	likely_pathogenic	0.9956	pathogenic	-1.087	Destabilizing	0.998	D	0.865	deleterious	None	None	disulfide	None	N
C/Q	0.9913	likely_pathogenic	0.9916	pathogenic	-1.516	Destabilizing	0.999	D	0.868	deleterious	None	None	disulfide	None	N
C/R	0.9774	likely_pathogenic	0.9795	pathogenic	-1.685	Destabilizing	0.997	D	0.862	deleterious	D	0.565459502	disulfide	None	N
C/S	0.7128	likely_pathogenic	0.7358	pathogenic	-2.298	Highly Destabilizing	0.961	D	0.768	deleterious	D	0.547101757	disulfide	None	N
C/T	0.7935	likely_pathogenic	0.8217	pathogenic	-1.881	Destabilizing	0.985	D	0.79	deleterious	None	None	disulfide	None	N
C/V	0.6205	likely_pathogenic	0.6141	pathogenic	-1.087	Destabilizing	0.985	D	0.767	deleterious	None	None	disulfide	None	N
C/W	0.9686	likely_pathogenic	0.9637	pathogenic	-1.444	Destabilizing	1.0	D	0.838	deleterious	D	0.565459502	disulfide	None	N
C/Y	0.9386	likely_pathogenic	0.9335	pathogenic	-1.281	Destabilizing	0.999	D	0.829	deleterious	D	0.553849707	disulfide	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.