TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4013	12262;12263;12264	chr2:178741196;178741195;178741194	chr2:179605923;179605922;179605921
N2AB	3696	11311;11312;11313	chr2:178741196;178741195;178741194	chr2:179605923;179605922;179605921
N2A	None	None	chr2:None	chr2:None
N2B	3650	11173;11174;11175	chr2:178741196;178741195;178741194	chr2:179605923;179605922;179605921
Novex-1	3775	11548;11549;11550	chr2:178741196;178741195;178741194	chr2:179605923;179605922;179605921
Novex-2	3842	11749;11750;11751	chr2:178741196;178741195;178741194	chr2:179605923;179605922;179605921
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-28
• Domain position: 76
• Structural Position: 158
• Q(SASA): 0.079
• 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
A/T	rs397517828	None	0.997	D	0.787	0.546	None	gnomAD-4.0.0	1.5925E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-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
A/C	0.9313	likely_pathogenic	0.8908	pathogenic	-1.773	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
A/D	0.9907	likely_pathogenic	0.9829	pathogenic	-3.019	Highly Destabilizing	0.995	D	0.868	deleterious	None	None	None	None	N
A/E	0.978	likely_pathogenic	0.9627	pathogenic	-2.893	Highly Destabilizing	0.997	D	0.839	deleterious	D	0.830703563	None	None	N
A/F	0.9673	likely_pathogenic	0.9495	pathogenic	-0.917	Destabilizing	0.999	D	0.902	deleterious	None	None	None	None	N
A/G	0.3636	ambiguous	0.3283	benign	-1.744	Destabilizing	0.117	N	0.359	neutral	D	0.712230398	None	None	N
A/H	0.9959	likely_pathogenic	0.9917	pathogenic	-1.805	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
A/I	0.8689	likely_pathogenic	0.8242	pathogenic	-0.386	Destabilizing	0.999	D	0.879	deleterious	None	None	None	None	N
A/K	0.9962	likely_pathogenic	0.9931	pathogenic	-1.533	Destabilizing	0.995	D	0.845	deleterious	None	None	None	None	N
A/L	0.8394	likely_pathogenic	0.7911	pathogenic	-0.386	Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	N
A/M	0.885	likely_pathogenic	0.8397	pathogenic	-0.706	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
A/N	0.9882	likely_pathogenic	0.9767	pathogenic	-1.809	Destabilizing	0.995	D	0.873	deleterious	None	None	None	None	N
A/P	0.9927	likely_pathogenic	0.9846	pathogenic	-0.675	Destabilizing	0.999	D	0.879	deleterious	D	0.830703563	None	None	N
A/Q	0.984	likely_pathogenic	0.9753	pathogenic	-1.774	Destabilizing	0.999	D	0.878	deleterious	None	None	None	None	N
A/R	0.9868	likely_pathogenic	0.9795	pathogenic	-1.374	Destabilizing	0.998	D	0.875	deleterious	None	None	None	None	N
A/S	0.4414	ambiguous	0.3577	ambiguous	-2.12	Highly Destabilizing	0.977	D	0.566	neutral	D	0.760815492	None	None	N
A/T	0.6146	likely_pathogenic	0.6723	pathogenic	-1.898	Destabilizing	0.997	D	0.787	deleterious	D	0.776702479	None	None	N
A/V	0.568	likely_pathogenic	0.4917	ambiguous	-0.675	Destabilizing	0.989	D	0.706	prob.neutral	D	0.590685667	None	None	N
A/W	0.9968	likely_pathogenic	0.9939	pathogenic	-1.526	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
A/Y	0.9885	likely_pathogenic	0.9802	pathogenic	-1.112	Destabilizing	1.0	D	0.899	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.