TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6995	21208;21209;21210	chr2:178724392;178724391;178724390	chr2:179589119;179589118;179589117
N2AB	6678	20257;20258;20259	chr2:178724392;178724391;178724390	chr2:179589119;179589118;179589117
N2A	5751	17476;17477;17478	chr2:178724392;178724391;178724390	chr2:179589119;179589118;179589117
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-54
• Domain position: 48
• Structural Position: 122
• Q(SASA): 0.6103
• 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	None	None	0.977	N	0.518	0.321	0.40017627803	gnomAD-4.0.0	6.84322E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99596E-07	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	0.3552	ambiguous	0.4027	ambiguous	-0.993	Destabilizing	0.983	D	0.566	neutral	None	None	None	None	N
K/C	0.712	likely_pathogenic	0.7262	pathogenic	-0.983	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
K/D	0.6668	likely_pathogenic	0.7094	pathogenic	-0.119	Destabilizing	0.998	D	0.695	prob.neutral	None	None	None	None	N
K/E	0.2285	likely_benign	0.261	benign	0.046	Stabilizing	0.977	D	0.518	neutral	N	0.48297744	None	None	N
K/F	0.7507	likely_pathogenic	0.7662	pathogenic	-0.608	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
K/G	0.5386	ambiguous	0.5751	pathogenic	-1.392	Destabilizing	0.998	D	0.55	neutral	None	None	None	None	N
K/H	0.2545	likely_benign	0.2551	benign	-1.612	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
K/I	0.2708	likely_benign	0.3132	benign	0.07	Stabilizing	0.997	D	0.709	prob.delet.	N	0.511646909	None	None	N
K/L	0.3621	ambiguous	0.3928	ambiguous	0.07	Stabilizing	0.995	D	0.55	neutral	None	None	None	None	N
K/M	0.2257	likely_benign	0.2546	benign	-0.063	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	N
K/N	0.4653	ambiguous	0.4938	ambiguous	-0.68	Destabilizing	0.993	D	0.619	neutral	N	0.509913326	None	None	N
K/P	0.9068	likely_pathogenic	0.9199	pathogenic	-0.256	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
K/Q	0.1243	likely_benign	0.1299	benign	-0.684	Destabilizing	0.993	D	0.609	neutral	N	0.442477612	None	None	N
K/R	0.0769	likely_benign	0.0791	benign	-0.616	Destabilizing	0.235	N	0.248	neutral	N	0.463410245	None	None	N
K/S	0.4019	ambiguous	0.4354	ambiguous	-1.487	Destabilizing	0.983	D	0.572	neutral	None	None	None	None	N
K/T	0.1437	likely_benign	0.1715	benign	-1.088	Destabilizing	0.997	D	0.643	neutral	N	0.482401437	None	None	N
K/V	0.2727	likely_benign	0.3164	benign	-0.256	Destabilizing	0.998	D	0.679	prob.neutral	None	None	None	None	N
K/W	0.7518	likely_pathogenic	0.7616	pathogenic	-0.418	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
K/Y	0.5437	ambiguous	0.5492	ambiguous	-0.118	Destabilizing	0.999	D	0.673	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.