TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28841	86746;86747;86748	chr2:178559611;178559610;178559609	chr2:179424338;179424337;179424336
N2AB	27200	81823;81824;81825	chr2:178559611;178559610;178559609	chr2:179424338;179424337;179424336
N2A	26273	79042;79043;79044	chr2:178559611;178559610;178559609	chr2:179424338;179424337;179424336
N2B	19776	59551;59552;59553	chr2:178559611;178559610;178559609	chr2:179424338;179424337;179424336
Novex-1	19901	59926;59927;59928	chr2:178559611;178559610;178559609	chr2:179424338;179424337;179424336
Novex-2	19968	60127;60128;60129	chr2:178559611;178559610;178559609	chr2:179424338;179424337;179424336
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-144
• Domain position: 87
• Structural Position: 175
• Q(SASA): 0.4689
• 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	rs879227926	None	0.998	D	0.629	0.338	0.218845423259	gnomAD-4.0.0	1.59126E-06	None	None	None	None	N	None	0	0	None	4.76735E-05	0	None	0	0	0	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	0.9231	likely_pathogenic	0.919	pathogenic	-0.446	Destabilizing	0.996	D	0.612	neutral	None	None	None	None	N
K/C	0.9475	likely_pathogenic	0.9477	pathogenic	-0.592	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
K/D	0.9525	likely_pathogenic	0.9498	pathogenic	0.137	Stabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
K/E	0.7903	likely_pathogenic	0.7676	pathogenic	0.252	Stabilizing	0.989	D	0.559	neutral	D	0.525285423	None	None	N
K/F	0.9847	likely_pathogenic	0.9845	pathogenic	-0.139	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
K/G	0.9636	likely_pathogenic	0.9619	pathogenic	-0.801	Destabilizing	0.999	D	0.642	neutral	None	None	None	None	N
K/H	0.6184	likely_pathogenic	0.5899	pathogenic	-1.017	Destabilizing	1.0	D	0.636	neutral	None	None	None	None	N
K/I	0.8956	likely_pathogenic	0.8933	pathogenic	0.467	Stabilizing	0.999	D	0.735	prob.delet.	N	0.513647064	None	None	N
K/L	0.8556	likely_pathogenic	0.8513	pathogenic	0.467	Stabilizing	0.999	D	0.642	neutral	None	None	None	None	N
K/M	0.7541	likely_pathogenic	0.747	pathogenic	0.172	Stabilizing	1.0	D	0.629	neutral	None	None	None	None	N
K/N	0.8957	likely_pathogenic	0.8868	pathogenic	-0.397	Destabilizing	0.998	D	0.629	neutral	D	0.52218919	None	None	N
K/P	0.9948	likely_pathogenic	0.9951	pathogenic	0.193	Stabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
K/Q	0.4703	ambiguous	0.4408	ambiguous	-0.411	Destabilizing	0.997	D	0.635	neutral	N	0.483072664	None	None	N
K/R	0.1129	likely_benign	0.1088	benign	-0.473	Destabilizing	0.217	N	0.279	neutral	N	0.454657476	None	None	N
K/S	0.9178	likely_pathogenic	0.9102	pathogenic	-1.056	Destabilizing	0.996	D	0.603	neutral	None	None	None	None	N
K/T	0.7032	likely_pathogenic	0.6842	pathogenic	-0.732	Destabilizing	0.998	D	0.677	prob.neutral	N	0.508699817	None	None	N
K/V	0.8531	likely_pathogenic	0.8499	pathogenic	0.193	Stabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
K/W	0.9631	likely_pathogenic	0.9641	pathogenic	-0.042	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
K/Y	0.942	likely_pathogenic	0.939	pathogenic	0.256	Stabilizing	1.0	D	0.702	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.