TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16696	50311;50312;50313	chr2:178612439;178612438;178612437	chr2:179477166;179477165;179477164
N2AB	15055	45388;45389;45390	chr2:178612439;178612438;178612437	chr2:179477166;179477165;179477164
N2A	14128	42607;42608;42609	chr2:178612439;178612438;178612437	chr2:179477166;179477165;179477164
N2B	7631	23116;23117;23118	chr2:178612439;178612438;178612437	chr2:179477166;179477165;179477164
Novex-1	7756	23491;23492;23493	chr2:178612439;178612438;178612437	chr2:179477166;179477165;179477164
Novex-2	7823	23692;23693;23694	chr2:178612439;178612438;178612437	chr2:179477166;179477165;179477164
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: Fn3-9
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.8702
• 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	rs745412383	0.215	1.0	N	0.657	0.276	0.207176502487	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9E-06	0
K/N	rs745412383	0.215	1.0	N	0.657	0.276	0.207176502487	gnomAD-4.0.0	1.59406E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86234E-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	0.9023	likely_pathogenic	0.9289	pathogenic	-0.122	Destabilizing	0.999	D	0.619	neutral	None	None	None	None	N
K/C	0.9768	likely_pathogenic	0.9806	pathogenic	-0.654	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
K/D	0.9534	likely_pathogenic	0.973	pathogenic	-0.431	Destabilizing	1.0	D	0.635	neutral	None	None	None	None	N
K/E	0.8593	likely_pathogenic	0.9244	pathogenic	-0.457	Destabilizing	0.999	D	0.631	neutral	N	0.474728982	None	None	N
K/F	0.986	likely_pathogenic	0.99	pathogenic	-0.52	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
K/G	0.871	likely_pathogenic	0.9011	pathogenic	-0.208	Destabilizing	1.0	D	0.607	neutral	None	None	None	None	N
K/H	0.7735	likely_pathogenic	0.8163	pathogenic	-0.249	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
K/I	0.9325	likely_pathogenic	0.9543	pathogenic	0.02	Stabilizing	1.0	D	0.715	prob.delet.	D	0.532352098	None	None	N
K/L	0.8869	likely_pathogenic	0.9071	pathogenic	0.02	Stabilizing	1.0	D	0.607	neutral	None	None	None	None	N
K/M	0.8561	likely_pathogenic	0.8899	pathogenic	-0.278	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	N
K/N	0.917	likely_pathogenic	0.9421	pathogenic	-0.216	Destabilizing	1.0	D	0.657	neutral	N	0.477141792	None	None	N
K/P	0.9037	likely_pathogenic	0.9369	pathogenic	-0.008	Destabilizing	1.0	D	0.624	neutral	None	None	None	None	N
K/Q	0.5825	likely_pathogenic	0.6709	pathogenic	-0.353	Destabilizing	1.0	D	0.648	neutral	N	0.468758841	None	None	N
K/R	0.1524	likely_benign	0.1444	benign	-0.278	Destabilizing	0.999	D	0.582	neutral	N	0.477881434	None	None	N
K/S	0.9182	likely_pathogenic	0.9434	pathogenic	-0.56	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
K/T	0.7848	likely_pathogenic	0.8443	pathogenic	-0.488	Destabilizing	1.0	D	0.619	neutral	N	0.478251311	None	None	N
K/V	0.9068	likely_pathogenic	0.9297	pathogenic	-0.008	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
K/W	0.9749	likely_pathogenic	0.9841	pathogenic	-0.629	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
K/Y	0.9619	likely_pathogenic	0.9702	pathogenic	-0.298	Destabilizing	1.0	D	0.681	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.