TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2588	7987;7988;7989	chr2:178773202;178773201;178773200	chr2:179637929;179637928;179637927
N2AB	2588	7987;7988;7989	chr2:178773202;178773201;178773200	chr2:179637929;179637928;179637927
N2A	2588	7987;7988;7989	chr2:178773202;178773201;178773200	chr2:179637929;179637928;179637927
N2B	2542	7849;7850;7851	chr2:178773202;178773201;178773200	chr2:179637929;179637928;179637927
Novex-1	2542	7849;7850;7851	chr2:178773202;178773201;178773200	chr2:179637929;179637928;179637927
Novex-2	2542	7849;7850;7851	chr2:178773202;178773201;178773200	chr2:179637929;179637928;179637927
Novex-3	2588	7987;7988;7989	chr2:178773202;178773201;178773200	chr2:179637929;179637928;179637927

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-15
• Domain position: 56
• Structural Position: 137
• Q(SASA): 0.3218
• 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	rs1361032185	None	0.801	D	0.505	0.189	0.210429274316	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07211E-04	0
K/N	rs1361032185	None	0.801	D	0.505	0.189	0.210429274316	gnomAD-4.0.0	6.57142E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.07211E-04	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	0.6094	likely_pathogenic	0.5584	ambiguous	-1.015	Destabilizing	0.525	D	0.47	neutral	None	None	None	None	N
K/C	0.7451	likely_pathogenic	0.7246	pathogenic	-1.201	Destabilizing	0.998	D	0.668	neutral	None	None	None	None	N
K/D	0.9029	likely_pathogenic	0.8567	pathogenic	-1.538	Destabilizing	0.842	D	0.517	neutral	None	None	None	None	N
K/E	0.3656	ambiguous	0.3052	benign	-1.306	Destabilizing	0.625	D	0.559	neutral	N	0.50892316	None	None	N
K/F	0.8916	likely_pathogenic	0.8595	pathogenic	-0.176	Destabilizing	0.974	D	0.654	neutral	None	None	None	None	N
K/G	0.7787	likely_pathogenic	0.722	pathogenic	-1.473	Destabilizing	0.842	D	0.591	neutral	None	None	None	None	N
K/H	0.373	ambiguous	0.3526	ambiguous	-1.778	Destabilizing	0.991	D	0.593	neutral	None	None	None	None	N
K/I	0.52	ambiguous	0.4457	ambiguous	0.251	Stabilizing	0.934	D	0.645	neutral	N	0.513302393	None	None	N
K/L	0.5576	ambiguous	0.5071	ambiguous	0.251	Stabilizing	0.728	D	0.573	neutral	None	None	None	None	N
K/M	0.3767	ambiguous	0.3365	benign	-0.062	Destabilizing	0.991	D	0.592	neutral	None	None	None	None	N
K/N	0.674	likely_pathogenic	0.5942	pathogenic	-1.652	Destabilizing	0.801	D	0.505	neutral	D	0.547251361	None	None	N
K/P	0.9904	likely_pathogenic	0.9852	pathogenic	-0.147	Destabilizing	0.974	D	0.575	neutral	None	None	None	None	N
K/Q	0.1706	likely_benign	0.1617	benign	-1.37	Destabilizing	0.801	D	0.551	neutral	N	0.512854558	None	None	N
K/R	0.0912	likely_benign	0.0887	benign	-1.415	Destabilizing	0.012	N	0.395	neutral	N	0.501550173	None	None	N
K/S	0.5713	likely_pathogenic	0.514	ambiguous	-2.084	Highly Destabilizing	0.08	N	0.291	neutral	None	None	None	None	N
K/T	0.2228	likely_benign	0.1958	benign	-1.626	Destabilizing	0.051	N	0.362	neutral	N	0.443957087	None	None	N
K/V	0.5104	ambiguous	0.4478	ambiguous	-0.147	Destabilizing	0.728	D	0.557	neutral	None	None	None	None	N
K/W	0.8694	likely_pathogenic	0.8429	pathogenic	-0.318	Destabilizing	0.998	D	0.699	prob.neutral	None	None	None	None	N
K/Y	0.7463	likely_pathogenic	0.6985	pathogenic	0.02	Stabilizing	0.991	D	0.64	neutral	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.