TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8932	27019;27020;27021	chr2:178713340;178713339;178713338	chr2:179578067;179578066;179578065
N2AB	8615	26068;26069;26070	chr2:178713340;178713339;178713338	chr2:179578067;179578066;179578065
N2A	7688	23287;23288;23289	chr2:178713340;178713339;178713338	chr2:179578067;179578066;179578065
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: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-75
• Domain position: 7
• Structural Position: 8
• 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
L/F	None	None	1.0	N	0.748	0.385	0.50143340055	gnomAD-4.0.0	3.50549E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.14062E-06	0	3.23562E-05
L/S	rs2154296552	None	1.0	N	0.866	0.476	0.748157190483	gnomAD-3.1.2	6.59E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07727E-04	0
L/S	rs2154296552	None	1.0	N	0.866	0.476	0.748157190483	gnomAD-4.0.0	6.58016E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.079E-04	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	0.8915	likely_pathogenic	0.9328	pathogenic	-2.177	Highly Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
L/C	0.9309	likely_pathogenic	0.9594	pathogenic	-1.374	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
L/D	0.9968	likely_pathogenic	0.9981	pathogenic	-2.015	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
L/E	0.9782	likely_pathogenic	0.9856	pathogenic	-1.957	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
L/F	0.6617	likely_pathogenic	0.77	pathogenic	-1.538	Destabilizing	1.0	D	0.748	deleterious	N	0.47689115	None	None	N
L/G	0.9695	likely_pathogenic	0.98	pathogenic	-2.579	Highly Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
L/H	0.9649	likely_pathogenic	0.9824	pathogenic	-1.874	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
L/I	0.2519	likely_benign	0.3139	benign	-1.093	Destabilizing	0.999	D	0.557	neutral	None	None	None	None	N
L/K	0.9631	likely_pathogenic	0.9761	pathogenic	-1.487	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
L/M	0.2841	likely_benign	0.3264	benign	-0.811	Destabilizing	1.0	D	0.763	deleterious	N	0.462002899	None	None	N
L/N	0.9796	likely_pathogenic	0.986	pathogenic	-1.388	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
L/P	0.6327	likely_pathogenic	0.7953	pathogenic	-1.428	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
L/Q	0.9089	likely_pathogenic	0.9424	pathogenic	-1.527	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
L/R	0.9315	likely_pathogenic	0.961	pathogenic	-0.938	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
L/S	0.9778	likely_pathogenic	0.9883	pathogenic	-2.042	Highly Destabilizing	1.0	D	0.866	deleterious	N	0.478625897	None	None	N
L/T	0.9318	likely_pathogenic	0.9592	pathogenic	-1.862	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
L/V	0.3324	likely_benign	0.4251	ambiguous	-1.428	Destabilizing	0.999	D	0.54	neutral	N	0.487740476	None	None	N
L/W	0.8778	likely_pathogenic	0.9317	pathogenic	-1.711	Destabilizing	1.0	D	0.783	deleterious	N	0.518975463	None	None	N
L/Y	0.951	likely_pathogenic	0.9727	pathogenic	-1.486	Destabilizing	1.0	D	0.849	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.