TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31546	94861;94862;94863	chr2:178546792;178546791;178546790	chr2:179411519;179411518;179411517
N2AB	29905	89938;89939;89940	chr2:178546792;178546791;178546790	chr2:179411519;179411518;179411517
N2A	28978	87157;87158;87159	chr2:178546792;178546791;178546790	chr2:179411519;179411518;179411517
N2B	22481	67666;67667;67668	chr2:178546792;178546791;178546790	chr2:179411519;179411518;179411517
Novex-1	22606	68041;68042;68043	chr2:178546792;178546791;178546790	chr2:179411519;179411518;179411517
Novex-2	22673	68242;68243;68244	chr2:178546792;178546791;178546790	chr2:179411519;179411518;179411517
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-118
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.0863
• 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/Q	rs746533506	-1.853	1.0	N	0.71	0.411	0.257786959452	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	1.29299E-04	0	None	0	0	None	0	None	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	0.936	likely_pathogenic	0.9325	pathogenic	-1.113	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
K/C	0.874	likely_pathogenic	0.8687	pathogenic	-1.086	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
K/D	0.9939	likely_pathogenic	0.9921	pathogenic	-0.953	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
K/E	0.8561	likely_pathogenic	0.8352	pathogenic	-0.706	Destabilizing	0.999	D	0.625	neutral	N	0.472938947	None	None	N
K/F	0.955	likely_pathogenic	0.9508	pathogenic	-0.362	Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
K/G	0.9581	likely_pathogenic	0.9535	pathogenic	-1.578	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
K/H	0.6218	likely_pathogenic	0.6177	pathogenic	-1.583	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
K/I	0.8481	likely_pathogenic	0.8292	pathogenic	0.175	Stabilizing	1.0	D	0.929	deleterious	None	None	None	None	N
K/L	0.7175	likely_pathogenic	0.6995	pathogenic	0.175	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
K/M	0.6091	likely_pathogenic	0.5915	pathogenic	-0.175	Destabilizing	1.0	D	0.801	deleterious	N	0.470549545	None	None	N
K/N	0.952	likely_pathogenic	0.9476	pathogenic	-1.23	Destabilizing	1.0	D	0.727	prob.delet.	N	0.476118952	None	None	N
K/P	0.998	likely_pathogenic	0.9977	pathogenic	-0.23	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
K/Q	0.3448	ambiguous	0.3462	ambiguous	-1.013	Destabilizing	1.0	D	0.71	prob.delet.	N	0.488812043	None	None	N
K/R	0.0959	likely_benign	0.0983	benign	-0.77	Destabilizing	0.999	D	0.594	neutral	N	0.395363164	None	None	N
K/S	0.9627	likely_pathogenic	0.9592	pathogenic	-1.854	Destabilizing	0.999	D	0.614	neutral	None	None	None	None	N
K/T	0.9001	likely_pathogenic	0.8922	pathogenic	-1.36	Destabilizing	1.0	D	0.773	deleterious	N	0.489855114	None	None	N
K/V	0.8424	likely_pathogenic	0.8242	pathogenic	-0.23	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
K/W	0.9467	likely_pathogenic	0.9379	pathogenic	-0.321	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
K/Y	0.869	likely_pathogenic	0.8564	pathogenic	0.002	Stabilizing	1.0	D	0.891	deleterious	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.