TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16688	50287;50288;50289	chr2:178612463;178612462;178612461	chr2:179477190;179477189;179477188
N2AB	15047	45364;45365;45366	chr2:178612463;178612462;178612461	chr2:179477190;179477189;179477188
N2A	14120	42583;42584;42585	chr2:178612463;178612462;178612461	chr2:179477190;179477189;179477188
N2B	7623	23092;23093;23094	chr2:178612463;178612462;178612461	chr2:179477190;179477189;179477188
Novex-1	7748	23467;23468;23469	chr2:178612463;178612462;178612461	chr2:179477190;179477189;179477188
Novex-2	7815	23668;23669;23670	chr2:178612463;178612462;178612461	chr2:179477190;179477189;179477188
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-9
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.0883
• 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
V/E	None	None	1.0	D	0.869	0.773	0.891958202521	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
V/A	0.9253	likely_pathogenic	0.9682	pathogenic	-2.726	Highly Destabilizing	0.999	D	0.613	neutral	D	0.722010265	None	None	N
V/C	0.9843	likely_pathogenic	0.9868	pathogenic	-2.307	Highly Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
V/D	0.9995	likely_pathogenic	0.9998	pathogenic	-3.694	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/E	0.9966	likely_pathogenic	0.9987	pathogenic	-3.387	Highly Destabilizing	1.0	D	0.869	deleterious	D	0.780505903	None	None	N
V/F	0.9291	likely_pathogenic	0.9689	pathogenic	-1.5	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
V/G	0.9839	likely_pathogenic	0.9936	pathogenic	-3.327	Highly Destabilizing	1.0	D	0.883	deleterious	D	0.780505903	None	None	N
V/H	0.9991	likely_pathogenic	0.9996	pathogenic	-3.078	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
V/I	0.1004	likely_benign	0.1086	benign	-0.97	Destabilizing	0.998	D	0.563	neutral	None	None	None	None	N
V/K	0.9962	likely_pathogenic	0.9985	pathogenic	-2.321	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
V/L	0.6715	likely_pathogenic	0.7714	pathogenic	-0.97	Destabilizing	0.997	D	0.623	neutral	N	0.50210207	None	None	N
V/M	0.8179	likely_pathogenic	0.9027	pathogenic	-1.234	Destabilizing	1.0	D	0.709	prob.delet.	D	0.685007628	None	None	N
V/N	0.998	likely_pathogenic	0.9992	pathogenic	-2.967	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
V/P	0.9967	likely_pathogenic	0.9983	pathogenic	-1.538	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
V/Q	0.9959	likely_pathogenic	0.9984	pathogenic	-2.639	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
V/R	0.992	likely_pathogenic	0.9966	pathogenic	-2.258	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
V/S	0.9883	likely_pathogenic	0.9957	pathogenic	-3.515	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
V/T	0.9133	likely_pathogenic	0.958	pathogenic	-3.058	Highly Destabilizing	0.999	D	0.64	neutral	None	None	None	None	N
V/W	0.9989	likely_pathogenic	0.9995	pathogenic	-2.092	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
V/Y	0.9956	likely_pathogenic	0.9981	pathogenic	-1.835	Destabilizing	1.0	D	0.793	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.