TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21967	66124;66125;66126	chr2:178582557;178582556;178582555	chr2:179447284;179447283;179447282
N2AB	20326	61201;61202;61203	chr2:178582557;178582556;178582555	chr2:179447284;179447283;179447282
N2A	19399	58420;58421;58422	chr2:178582557;178582556;178582555	chr2:179447284;179447283;179447282
N2B	12902	38929;38930;38931	chr2:178582557;178582556;178582555	chr2:179447284;179447283;179447282
Novex-1	13027	39304;39305;39306	chr2:178582557;178582556;178582555	chr2:179447284;179447283;179447282
Novex-2	13094	39505;39506;39507	chr2:178582557;178582556;178582555	chr2:179447284;179447283;179447282
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-47
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.6834
• 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/E	None	None	0.09	N	0.381	0.073	0.16115917748	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-06	0	0
K/N	None	None	0.001	N	0.109	0.073	0.115124310173	gnomAD-4.0.0	8.40225E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.18751E-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
K/A	0.4357	ambiguous	0.4152	ambiguous	-0.301	Destabilizing	0.207	N	0.333	neutral	None	None	None	None	N
K/C	0.6651	likely_pathogenic	0.6835	pathogenic	-0.326	Destabilizing	0.981	D	0.369	neutral	None	None	None	None	N
K/D	0.6021	likely_pathogenic	0.5711	pathogenic	-0.148	Destabilizing	0.241	N	0.327	neutral	None	None	None	None	N
K/E	0.2803	likely_benign	0.289	benign	-0.054	Destabilizing	0.09	N	0.381	neutral	N	0.365712261	None	None	N
K/F	0.8362	likely_pathogenic	0.8524	pathogenic	-0.101	Destabilizing	0.818	D	0.366	neutral	None	None	None	None	N
K/G	0.5483	ambiguous	0.5079	ambiguous	-0.615	Destabilizing	0.241	N	0.355	neutral	None	None	None	None	N
K/H	0.2283	likely_benign	0.2737	benign	-0.848	Destabilizing	0.002	N	0.13	neutral	None	None	None	None	N
K/I	0.5374	ambiguous	0.5381	ambiguous	0.492	Stabilizing	0.773	D	0.373	neutral	N	0.506648442	None	None	N
K/L	0.508	ambiguous	0.5319	ambiguous	0.492	Stabilizing	0.388	N	0.383	neutral	None	None	None	None	N
K/M	0.3757	ambiguous	0.3796	ambiguous	0.102	Stabilizing	0.981	D	0.339	neutral	None	None	None	None	N
K/N	0.4476	ambiguous	0.4236	ambiguous	-0.157	Destabilizing	0.001	N	0.109	neutral	N	0.390205273	None	None	N
K/P	0.9469	likely_pathogenic	0.937	pathogenic	0.257	Stabilizing	0.818	D	0.353	neutral	None	None	None	None	N
K/Q	0.1434	likely_benign	0.1542	benign	-0.164	Destabilizing	0.324	N	0.383	neutral	N	0.455776904	None	None	N
K/R	0.0883	likely_benign	0.0893	benign	-0.342	Destabilizing	0.001	N	0.125	neutral	N	0.415469077	None	None	N
K/S	0.4537	ambiguous	0.4363	ambiguous	-0.636	Destabilizing	0.241	N	0.336	neutral	None	None	None	None	N
K/T	0.2403	likely_benign	0.2344	benign	-0.353	Destabilizing	0.324	N	0.337	neutral	N	0.479037766	None	None	N
K/V	0.4381	ambiguous	0.4474	ambiguous	0.257	Stabilizing	0.69	D	0.338	neutral	None	None	None	None	N
K/W	0.828	likely_pathogenic	0.8507	pathogenic	-0.099	Destabilizing	0.981	D	0.445	neutral	None	None	None	None	N
K/Y	0.6418	likely_pathogenic	0.676	pathogenic	0.192	Stabilizing	0.69	D	0.341	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.