TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19593	59002;59003;59004	chr2:178593431;178593430;178593429	chr2:179458158;179458157;179458156
N2AB	17952	54079;54080;54081	chr2:178593431;178593430;178593429	chr2:179458158;179458157;179458156
N2A	17025	51298;51299;51300	chr2:178593431;178593430;178593429	chr2:179458158;179458157;179458156
N2B	10528	31807;31808;31809	chr2:178593431;178593430;178593429	chr2:179458158;179458157;179458156
Novex-1	10653	32182;32183;32184	chr2:178593431;178593430;178593429	chr2:179458158;179458157;179458156
Novex-2	10720	32383;32384;32385	chr2:178593431;178593430;178593429	chr2:179458158;179458157;179458156
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: Fn3-30
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.4214
• 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	rs1465047978	None	0.989	N	0.534	0.264	0.270889551736	gnomAD-4.0.0	3.42245E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49815E-06	0	0
K/N	None	None	0.989	N	0.571	0.197	0.241078983079	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.4547	ambiguous	0.4224	ambiguous	-0.226	Destabilizing	0.996	D	0.567	neutral	None	None	None	None	N
K/C	0.7324	likely_pathogenic	0.7096	pathogenic	-0.302	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
K/D	0.8884	likely_pathogenic	0.8717	pathogenic	-0.423	Destabilizing	0.999	D	0.599	neutral	None	None	None	None	N
K/E	0.4585	ambiguous	0.4011	ambiguous	-0.411	Destabilizing	0.989	D	0.534	neutral	N	0.511147398	None	None	N
K/F	0.9459	likely_pathogenic	0.941	pathogenic	-0.543	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	N
K/G	0.5142	ambiguous	0.4698	ambiguous	-0.467	Destabilizing	0.996	D	0.604	neutral	None	None	None	None	N
K/H	0.4672	ambiguous	0.4685	ambiguous	-0.991	Destabilizing	0.269	N	0.372	neutral	None	None	None	None	N
K/I	0.8287	likely_pathogenic	0.7981	pathogenic	0.34	Stabilizing	0.999	D	0.749	deleterious	N	0.487435578	None	None	N
K/L	0.7724	likely_pathogenic	0.7306	pathogenic	0.34	Stabilizing	0.999	D	0.591	neutral	None	None	None	None	N
K/M	0.5633	ambiguous	0.5075	ambiguous	0.532	Stabilizing	1.0	D	0.608	neutral	None	None	None	None	N
K/N	0.7441	likely_pathogenic	0.7086	pathogenic	-0.047	Destabilizing	0.989	D	0.571	neutral	N	0.514862493	None	None	N
K/P	0.9078	likely_pathogenic	0.8902	pathogenic	0.18	Stabilizing	1.0	D	0.636	neutral	None	None	None	None	N
K/Q	0.2446	likely_benign	0.2289	benign	-0.376	Destabilizing	0.998	D	0.603	neutral	N	0.471938216	None	None	N
K/R	0.0791	likely_benign	0.0729	benign	-0.133	Destabilizing	0.989	D	0.496	neutral	N	0.487811965	None	None	N
K/S	0.5579	ambiguous	0.5079	ambiguous	-0.566	Destabilizing	0.996	D	0.535	neutral	None	None	None	None	N
K/T	0.5251	ambiguous	0.4717	ambiguous	-0.398	Destabilizing	0.999	D	0.593	neutral	N	0.479949932	None	None	N
K/V	0.7283	likely_pathogenic	0.6885	pathogenic	0.18	Stabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
K/W	0.9166	likely_pathogenic	0.9015	pathogenic	-0.477	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
K/Y	0.8549	likely_pathogenic	0.8445	pathogenic	-0.077	Destabilizing	0.998	D	0.704	prob.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.