TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19369	58330;58331;58332	chr2:178594389;178594388;178594387	chr2:179459116;179459115;179459114
N2AB	17728	53407;53408;53409	chr2:178594389;178594388;178594387	chr2:179459116;179459115;179459114
N2A	16801	50626;50627;50628	chr2:178594389;178594388;178594387	chr2:179459116;179459115;179459114
N2B	10304	31135;31136;31137	chr2:178594389;178594388;178594387	chr2:179459116;179459115;179459114
Novex-1	10429	31510;31511;31512	chr2:178594389;178594388;178594387	chr2:179459116;179459115;179459114
Novex-2	10496	31711;31712;31713	chr2:178594389;178594388;178594387	chr2:179459116;179459115;179459114
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: Fn3-28
• Domain position: 86
• Structural Position: 119
• Q(SASA): 0.5294
• Predicted PPI site: I

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	rs759447234	None	0.999	N	0.696	0.395	0.259761712551	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
K/E	rs759447234	None	0.999	N	0.696	0.395	0.259761712551	gnomAD-4.0.0	1.43457E-05	None	None	None	None	I	None	0	1.70045E-05	None	0	0	None	0	0	1.53291E-05	0	6.45557E-05

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	0.8775	likely_pathogenic	0.8631	pathogenic	0.011	Stabilizing	0.999	D	0.757	deleterious	None	None	None	None	I
K/C	0.9549	likely_pathogenic	0.9492	pathogenic	-0.308	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	I
K/D	0.9489	likely_pathogenic	0.9339	pathogenic	0.111	Stabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
K/E	0.7784	likely_pathogenic	0.7176	pathogenic	0.127	Stabilizing	0.999	D	0.696	prob.neutral	N	0.443597041	None	None	I
K/F	0.975	likely_pathogenic	0.9592	pathogenic	-0.13	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	I
K/G	0.9387	likely_pathogenic	0.9271	pathogenic	-0.199	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
K/H	0.7867	likely_pathogenic	0.7426	pathogenic	-0.387	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	I
K/I	0.7948	likely_pathogenic	0.7403	pathogenic	0.485	Stabilizing	1.0	D	0.807	deleterious	N	0.473623737	None	None	I
K/L	0.7922	likely_pathogenic	0.7523	pathogenic	0.485	Stabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
K/M	0.7189	likely_pathogenic	0.6505	pathogenic	0.177	Stabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	I
K/N	0.8975	likely_pathogenic	0.8619	pathogenic	0.157	Stabilizing	1.0	D	0.77	deleterious	N	0.515094567	None	None	I
K/P	0.8607	likely_pathogenic	0.8651	pathogenic	0.355	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
K/Q	0.5319	ambiguous	0.4881	ambiguous	0.001	Stabilizing	1.0	D	0.761	deleterious	N	0.482886148	None	None	I
K/R	0.1722	likely_benign	0.1756	benign	-0.041	Destabilizing	0.999	D	0.682	prob.neutral	N	0.470495641	None	None	I
K/S	0.923	likely_pathogenic	0.9032	pathogenic	-0.347	Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	I
K/T	0.7623	likely_pathogenic	0.7211	pathogenic	-0.178	Destabilizing	1.0	D	0.79	deleterious	N	0.519500309	None	None	I
K/V	0.7828	likely_pathogenic	0.7454	pathogenic	0.355	Stabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
K/W	0.978	likely_pathogenic	0.9655	pathogenic	-0.133	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
K/Y	0.9305	likely_pathogenic	0.899	pathogenic	0.212	Stabilizing	1.0	D	0.792	deleterious	None	None	None	None	I

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.