TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28300	85123;85124;85125	chr2:178561234;178561233;178561232	chr2:179425961;179425960;179425959
N2AB	26659	80200;80201;80202	chr2:178561234;178561233;178561232	chr2:179425961;179425960;179425959
N2A	25732	77419;77420;77421	chr2:178561234;178561233;178561232	chr2:179425961;179425960;179425959
N2B	19235	57928;57929;57930	chr2:178561234;178561233;178561232	chr2:179425961;179425960;179425959
Novex-1	19360	58303;58304;58305	chr2:178561234;178561233;178561232	chr2:179425961;179425960;179425959
Novex-2	19427	58504;58505;58506	chr2:178561234;178561233;178561232	chr2:179425961;179425960;179425959
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-94
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.3896
• 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
L/P	rs1703551325	None	0.998	N	0.779	0.462	0.76634211205	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
L/P	rs1703551325	None	0.998	N	0.779	0.462	0.76634211205	gnomAD-4.0.0	6.57246E-06	None	None	None	None	N	None	2.41324E-05	0	None	0	0	None	0	0	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
L/A	0.4977	ambiguous	0.4387	ambiguous	-1.478	Destabilizing	0.968	D	0.598	neutral	None	None	None	None	N
L/C	0.6586	likely_pathogenic	0.6296	pathogenic	-0.763	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
L/D	0.9028	likely_pathogenic	0.8688	pathogenic	-0.999	Destabilizing	0.995	D	0.778	deleterious	None	None	None	None	N
L/E	0.5589	ambiguous	0.4889	ambiguous	-1.017	Destabilizing	0.991	D	0.771	deleterious	None	None	None	None	N
L/F	0.2722	likely_benign	0.2521	benign	-1.03	Destabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	N
L/G	0.7367	likely_pathogenic	0.6908	pathogenic	-1.769	Destabilizing	0.991	D	0.769	deleterious	None	None	None	None	N
L/H	0.3869	ambiguous	0.3337	benign	-0.941	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
L/I	0.1175	likely_benign	0.1143	benign	-0.765	Destabilizing	0.984	D	0.547	neutral	None	None	None	None	N
L/K	0.3855	ambiguous	0.335	benign	-1.035	Destabilizing	0.982	D	0.697	prob.neutral	None	None	None	None	N
L/M	0.1136	likely_benign	0.1049	benign	-0.565	Destabilizing	0.998	D	0.707	prob.neutral	N	0.425918144	None	None	N
L/N	0.5666	likely_pathogenic	0.5144	ambiguous	-0.803	Destabilizing	0.991	D	0.778	deleterious	None	None	None	None	N
L/P	0.9645	likely_pathogenic	0.9543	pathogenic	-0.971	Destabilizing	0.998	D	0.779	deleterious	N	0.485118173	None	None	N
L/Q	0.1911	likely_benign	0.1579	benign	-1.011	Destabilizing	0.988	D	0.757	deleterious	N	0.475304028	None	None	N
L/R	0.3419	ambiguous	0.2804	benign	-0.381	Destabilizing	0.142	N	0.411	neutral	N	0.494121862	None	None	N
L/S	0.5655	likely_pathogenic	0.4888	ambiguous	-1.347	Destabilizing	0.991	D	0.753	deleterious	None	None	None	None	N
L/T	0.3651	ambiguous	0.3	benign	-1.259	Destabilizing	0.991	D	0.725	prob.delet.	None	None	None	None	N
L/V	0.1239	likely_benign	0.1126	benign	-0.971	Destabilizing	0.979	D	0.559	neutral	N	0.457142341	None	None	N
L/W	0.482	ambiguous	0.4299	ambiguous	-1.091	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
L/Y	0.5182	ambiguous	0.4963	ambiguous	-0.886	Destabilizing	0.998	D	0.765	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.