TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14841	44746;44747;44748	chr2:178625300;178625299;178625298	chr2:179490027;179490026;179490025
N2AB	13200	39823;39824;39825	chr2:178625300;178625299;178625298	chr2:179490027;179490026;179490025
N2A	12273	37042;37043;37044	chr2:178625300;178625299;178625298	chr2:179490027;179490026;179490025
N2B	5776	17551;17552;17553	chr2:178625300;178625299;178625298	chr2:179490027;179490026;179490025
Novex-1	5901	17926;17927;17928	chr2:178625300;178625299;178625298	chr2:179490027;179490026;179490025
Novex-2	5968	18127;18128;18129	chr2:178625300;178625299;178625298	chr2:179490027;179490026;179490025
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: Ig-99
• Domain position: 77
• Structural Position: 163
• Q(SASA): 0.2541
• 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	rs2058863893	None	0.454	N	0.503	0.129	0.167679373172	gnomAD-4.0.0	3.43384E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80294E-06	3.51009E-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
K/A	0.4068	ambiguous	0.4093	ambiguous	-0.339	Destabilizing	0.688	D	0.475	neutral	None	None	None	None	N
K/C	0.663	likely_pathogenic	0.6653	pathogenic	-0.219	Destabilizing	0.998	D	0.552	neutral	None	None	None	None	N
K/D	0.7291	likely_pathogenic	0.722	pathogenic	0.022	Stabilizing	0.842	D	0.571	neutral	None	None	None	None	N
K/E	0.1969	likely_benign	0.2117	benign	0.102	Stabilizing	0.454	N	0.503	neutral	N	0.445482254	None	None	N
K/F	0.7869	likely_pathogenic	0.7776	pathogenic	-0.13	Destabilizing	0.949	D	0.579	neutral	None	None	None	None	N
K/G	0.6078	likely_pathogenic	0.5962	pathogenic	-0.656	Destabilizing	0.016	N	0.382	neutral	None	None	None	None	N
K/H	0.2967	likely_benign	0.2747	benign	-0.956	Destabilizing	0.974	D	0.58	neutral	None	None	None	None	N
K/I	0.3014	likely_benign	0.2998	benign	0.457	Stabilizing	0.876	D	0.586	neutral	N	0.439984316	None	None	N
K/L	0.3652	ambiguous	0.3605	ambiguous	0.457	Stabilizing	0.016	N	0.38	neutral	None	None	None	None	N
K/M	0.2214	likely_benign	0.2316	benign	0.202	Stabilizing	0.949	D	0.584	neutral	None	None	None	None	N
K/N	0.497	ambiguous	0.4854	ambiguous	-0.06	Destabilizing	0.801	D	0.539	neutral	N	0.43167024	None	None	N
K/P	0.8994	likely_pathogenic	0.8976	pathogenic	0.221	Stabilizing	0.991	D	0.625	neutral	None	None	None	None	N
K/Q	0.1166	likely_benign	0.1164	benign	-0.119	Destabilizing	0.136	N	0.211	neutral	N	0.440427789	None	None	N
K/R	0.0845	likely_benign	0.0816	benign	-0.357	Destabilizing	0.012	N	0.279	neutral	N	0.425738444	None	None	N
K/S	0.436	ambiguous	0.4125	ambiguous	-0.597	Destabilizing	0.842	D	0.507	neutral	None	None	None	None	N
K/T	0.1487	likely_benign	0.1487	benign	-0.33	Destabilizing	0.891	D	0.521	neutral	N	0.445695991	None	None	N
K/V	0.2937	likely_benign	0.2876	benign	0.221	Stabilizing	0.728	D	0.529	neutral	None	None	None	None	N
K/W	0.7945	likely_pathogenic	0.761	pathogenic	-0.08	Destabilizing	0.998	D	0.561	neutral	None	None	None	None	N
K/Y	0.6729	likely_pathogenic	0.6542	pathogenic	0.198	Stabilizing	0.991	D	0.581	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.