TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2516	7771;7772;7773	chr2:178773510;178773509;178773508	chr2:179638237;179638236;179638235
N2AB	2516	7771;7772;7773	chr2:178773510;178773509;178773508	chr2:179638237;179638236;179638235
N2A	2516	7771;7772;7773	chr2:178773510;178773509;178773508	chr2:179638237;179638236;179638235
N2B	2470	7633;7634;7635	chr2:178773510;178773509;178773508	chr2:179638237;179638236;179638235
Novex-1	2470	7633;7634;7635	chr2:178773510;178773509;178773508	chr2:179638237;179638236;179638235
Novex-2	2470	7633;7634;7635	chr2:178773510;178773509;178773508	chr2:179638237;179638236;179638235
Novex-3	2516	7771;7772;7773	chr2:178773510;178773509;178773508	chr2:179638237;179638236;179638235

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-14
• Domain position: 72
• Structural Position: 155
• Q(SASA): 0.1877
• 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
K/N	rs200973013	None	0.075	D	0.477	0.205	0.0716867268079	gnomAD-4.0.0	6.3629E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.14272E-05	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
K/A	0.5185	ambiguous	0.4873	ambiguous	-1.359	Destabilizing	0.633	D	0.657	neutral	None	None	None	None	N
K/C	0.6299	likely_pathogenic	0.6158	pathogenic	-1.623	Destabilizing	0.996	D	0.787	deleterious	None	None	None	None	N
K/D	0.8462	likely_pathogenic	0.8281	pathogenic	-1.648	Destabilizing	0.633	D	0.623	neutral	None	None	None	None	N
K/E	0.3787	ambiguous	0.3508	ambiguous	-1.391	Destabilizing	0.722	D	0.621	neutral	N	0.450463263	None	None	N
K/F	0.8305	likely_pathogenic	0.816	pathogenic	-0.698	Destabilizing	0.961	D	0.793	deleterious	None	None	None	None	N
K/G	0.675	likely_pathogenic	0.6453	pathogenic	-1.817	Destabilizing	0.775	D	0.657	neutral	None	None	None	None	N
K/H	0.2728	likely_benign	0.2595	benign	-1.995	Destabilizing	0.961	D	0.683	prob.neutral	None	None	None	None	N
K/I	0.4781	ambiguous	0.4501	ambiguous	-0.084	Destabilizing	0.858	D	0.767	deleterious	None	None	None	None	N
K/L	0.4763	ambiguous	0.4523	ambiguous	-0.084	Destabilizing	0.633	D	0.652	neutral	None	None	None	None	N
K/M	0.2986	likely_benign	0.2806	benign	-0.416	Destabilizing	0.986	D	0.673	neutral	N	0.431804713	None	None	N
K/N	0.5618	ambiguous	0.5327	ambiguous	-1.706	Destabilizing	0.075	N	0.477	neutral	D	0.575726966	None	None	N
K/P	0.9872	likely_pathogenic	0.9853	pathogenic	-0.485	Destabilizing	0.961	D	0.673	neutral	None	None	None	None	N
K/Q	0.1601	likely_benign	0.1539	benign	-1.468	Destabilizing	0.901	D	0.595	neutral	N	0.445738254	None	None	N
K/R	0.0835	likely_benign	0.0826	benign	-1.218	Destabilizing	0.008	N	0.478	neutral	N	0.447391698	None	None	N
K/S	0.4686	ambiguous	0.4442	ambiguous	-2.273	Highly Destabilizing	0.633	D	0.595	neutral	None	None	None	None	N
K/T	0.1836	likely_benign	0.1681	benign	-1.768	Destabilizing	0.008	N	0.503	neutral	N	0.42714084	None	None	N
K/V	0.4477	ambiguous	0.4232	ambiguous	-0.485	Destabilizing	0.858	D	0.687	prob.neutral	None	None	None	None	N
K/W	0.8194	likely_pathogenic	0.8082	pathogenic	-0.721	Destabilizing	0.996	D	0.767	deleterious	None	None	None	None	N
K/Y	0.6818	likely_pathogenic	0.6624	pathogenic	-0.36	Destabilizing	0.987	D	0.746	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.