TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1321	4186;4187;4188	chr2:178779231;178779230;178779229	chr2:179643958;179643957;179643956
N2AB	1321	4186;4187;4188	chr2:178779231;178779230;178779229	chr2:179643958;179643957;179643956
N2A	1321	4186;4187;4188	chr2:178779231;178779230;178779229	chr2:179643958;179643957;179643956
N2B	1275	4048;4049;4050	chr2:178779231;178779230;178779229	chr2:179643958;179643957;179643956
Novex-1	1275	4048;4049;4050	chr2:178779231;178779230;178779229	chr2:179643958;179643957;179643956
Novex-2	1275	4048;4049;4050	chr2:178779231;178779230;178779229	chr2:179643958;179643957;179643956
Novex-3	1321	4186;4187;4188	chr2:178779231;178779230;178779229	chr2:179643958;179643957;179643956

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-5
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.7981
• 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	rs1204400340	0.441	0.999	N	0.662	0.505	0.435152311215	gnomAD-2.1.1	4.01E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
K/E	rs1204400340	0.441	0.999	N	0.662	0.505	0.435152311215	gnomAD-4.0.0	2.40103E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.62544E-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	0.891	likely_pathogenic	0.8684	pathogenic	-0.161	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	I
K/C	0.9688	likely_pathogenic	0.965	pathogenic	-0.366	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	I
K/D	0.9783	likely_pathogenic	0.972	pathogenic	0.216	Stabilizing	1.0	D	0.774	deleterious	None	None	None	None	I
K/E	0.7727	likely_pathogenic	0.7322	pathogenic	0.275	Stabilizing	0.999	D	0.662	neutral	N	0.473135512	None	None	I
K/F	0.9886	likely_pathogenic	0.9869	pathogenic	-0.176	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
K/G	0.9496	likely_pathogenic	0.9354	pathogenic	-0.417	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
K/H	0.7737	likely_pathogenic	0.7533	pathogenic	-0.606	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
K/I	0.8808	likely_pathogenic	0.8724	pathogenic	0.454	Stabilizing	1.0	D	0.786	deleterious	None	None	None	None	I
K/L	0.8692	likely_pathogenic	0.8576	pathogenic	0.454	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
K/M	0.8147	likely_pathogenic	0.8036	pathogenic	0.073	Stabilizing	1.0	D	0.751	deleterious	D	0.549640346	None	None	I
K/N	0.9473	likely_pathogenic	0.937	pathogenic	0.046	Stabilizing	1.0	D	0.761	deleterious	N	0.511333319	None	None	I
K/P	0.9904	likely_pathogenic	0.9862	pathogenic	0.278	Stabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
K/Q	0.5245	ambiguous	0.4861	ambiguous	-0.015	Destabilizing	1.0	D	0.741	deleterious	N	0.508906	None	None	I
K/R	0.1488	likely_benign	0.1386	benign	-0.105	Destabilizing	0.999	D	0.605	neutral	N	0.513531673	None	None	I
K/S	0.9289	likely_pathogenic	0.9156	pathogenic	-0.495	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	I
K/T	0.7545	likely_pathogenic	0.7372	pathogenic	-0.257	Destabilizing	1.0	D	0.744	deleterious	N	0.49304959	None	None	I
K/V	0.7873	likely_pathogenic	0.7761	pathogenic	0.278	Stabilizing	1.0	D	0.752	deleterious	None	None	None	None	I
K/W	0.9878	likely_pathogenic	0.9848	pathogenic	-0.171	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
K/Y	0.9622	likely_pathogenic	0.9588	pathogenic	0.161	Stabilizing	1.0	D	0.769	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.