TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1911	5956;5957;5958	chr2:178776133;178776132;178776131	chr2:179640860;179640859;179640858
N2AB	1911	5956;5957;5958	chr2:178776133;178776132;178776131	chr2:179640860;179640859;179640858
N2A	1911	5956;5957;5958	chr2:178776133;178776132;178776131	chr2:179640860;179640859;179640858
N2B	1865	5818;5819;5820	chr2:178776133;178776132;178776131	chr2:179640860;179640859;179640858
Novex-1	1865	5818;5819;5820	chr2:178776133;178776132;178776131	chr2:179640860;179640859;179640858
Novex-2	1865	5818;5819;5820	chr2:178776133;178776132;178776131	chr2:179640860;179640859;179640858
Novex-3	1911	5956;5957;5958	chr2:178776133;178776132;178776131	chr2:179640860;179640859;179640858

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-9
• Domain position: 71
• Structural Position: 155
• Q(SASA): 0.176
• 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/T	rs1473622038	None	0.722	N	0.493	0.145	0.148003135375	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/T	rs1473622038	None	0.722	N	0.493	0.145	0.148003135375	gnomAD-4.0.0	6.56978E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.4699E-05	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	0.6186	likely_pathogenic	0.7821	pathogenic	-1.28	Destabilizing	0.775	D	0.501	neutral	None	None	None	None	N
K/C	0.7405	likely_pathogenic	0.8009	pathogenic	-1.509	Destabilizing	0.996	D	0.747	deleterious	None	None	None	None	N
K/D	0.9669	likely_pathogenic	0.9843	pathogenic	-1.533	Destabilizing	0.923	D	0.54	neutral	None	None	None	None	N
K/E	0.5849	likely_pathogenic	0.7705	pathogenic	-1.299	Destabilizing	0.722	D	0.509	neutral	N	0.421454695	None	None	N
K/F	0.908	likely_pathogenic	0.9504	pathogenic	-0.589	Destabilizing	0.987	D	0.739	prob.delet.	None	None	None	None	N
K/G	0.8622	likely_pathogenic	0.9266	pathogenic	-1.713	Destabilizing	0.775	D	0.555	neutral	None	None	None	None	N
K/H	0.4936	ambiguous	0.5775	pathogenic	-1.916	Destabilizing	0.961	D	0.62	neutral	None	None	None	None	N
K/I	0.4667	ambiguous	0.6186	pathogenic	-0.082	Destabilizing	0.961	D	0.737	prob.delet.	None	None	None	None	N
K/L	0.5162	ambiguous	0.6516	pathogenic	-0.082	Destabilizing	0.775	D	0.555	neutral	None	None	None	None	N
K/M	0.2874	likely_benign	0.4478	ambiguous	-0.47	Destabilizing	0.995	D	0.615	neutral	N	0.419960877	None	None	N
K/N	0.8315	likely_pathogenic	0.9121	pathogenic	-1.605	Destabilizing	0.722	D	0.444	neutral	N	0.468600584	None	None	N
K/P	0.997	likely_pathogenic	0.9984	pathogenic	-0.458	Destabilizing	0.987	D	0.593	neutral	None	None	None	None	N
K/Q	0.2357	likely_benign	0.3483	ambiguous	-1.397	Destabilizing	0.722	D	0.474	neutral	N	0.419957366	None	None	N
K/R	0.1045	likely_benign	0.1109	benign	-1.233	Destabilizing	0.003	N	0.233	neutral	N	0.394262974	None	None	N
K/S	0.7193	likely_pathogenic	0.8511	pathogenic	-2.132	Highly Destabilizing	0.775	D	0.421	neutral	None	None	None	None	N
K/T	0.2562	likely_benign	0.4257	ambiguous	-1.67	Destabilizing	0.722	D	0.493	neutral	N	0.390947342	None	None	N
K/V	0.4117	ambiguous	0.5329	ambiguous	-0.458	Destabilizing	0.961	D	0.59	neutral	None	None	None	None	N
K/W	0.8948	likely_pathogenic	0.935	pathogenic	-0.629	Destabilizing	0.996	D	0.728	prob.delet.	None	None	None	None	N
K/Y	0.8355	likely_pathogenic	0.9014	pathogenic	-0.278	Destabilizing	0.987	D	0.693	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.