TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22336	67231;67232;67233	chr2:178580373;178580372;178580371	chr2:179445100;179445099;179445098
N2AB	20695	62308;62309;62310	chr2:178580373;178580372;178580371	chr2:179445100;179445099;179445098
N2A	19768	59527;59528;59529	chr2:178580373;178580372;178580371	chr2:179445100;179445099;179445098
N2B	13271	40036;40037;40038	chr2:178580373;178580372;178580371	chr2:179445100;179445099;179445098
Novex-1	13396	40411;40412;40413	chr2:178580373;178580372;178580371	chr2:179445100;179445099;179445098
Novex-2	13463	40612;40613;40614	chr2:178580373;178580372;178580371	chr2:179445100;179445099;179445098
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: Ig-126
• Domain position: 72
• Structural Position: 158
• Q(SASA): 0.1164
• 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	None	None	1.0	N	0.743	0.787	0.889071410426	gnomAD-4.0.0	3.4222E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49853E-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
L/A	0.6278	likely_pathogenic	0.6327	pathogenic	-2.698	Highly Destabilizing	0.999	D	0.649	neutral	None	None	None	None	N
L/C	0.8312	likely_pathogenic	0.8191	pathogenic	-2.003	Highly Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
L/D	0.9991	likely_pathogenic	0.9992	pathogenic	-3.142	Highly Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
L/E	0.9911	likely_pathogenic	0.9918	pathogenic	-2.934	Highly Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
L/F	0.8106	likely_pathogenic	0.7939	pathogenic	-1.647	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
L/G	0.9694	likely_pathogenic	0.9725	pathogenic	-3.23	Highly Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
L/H	0.9919	likely_pathogenic	0.992	pathogenic	-2.679	Highly Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
L/I	0.1666	likely_benign	0.1467	benign	-1.163	Destabilizing	0.999	D	0.503	neutral	None	None	None	None	N
L/K	0.9918	likely_pathogenic	0.993	pathogenic	-2.246	Highly Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
L/M	0.2377	likely_benign	0.2126	benign	-1.078	Destabilizing	1.0	D	0.757	deleterious	N	0.495758869	None	None	N
L/N	0.993	likely_pathogenic	0.9939	pathogenic	-2.545	Highly Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
L/P	0.9968	likely_pathogenic	0.9975	pathogenic	-1.656	Destabilizing	1.0	D	0.743	deleterious	N	0.514116613	None	None	N
L/Q	0.9642	likely_pathogenic	0.9667	pathogenic	-2.442	Highly Destabilizing	1.0	D	0.756	deleterious	N	0.514116613	None	None	N
L/R	0.983	likely_pathogenic	0.985	pathogenic	-1.847	Destabilizing	1.0	D	0.749	deleterious	N	0.514116613	None	None	N
L/S	0.9547	likely_pathogenic	0.9563	pathogenic	-3.207	Highly Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
L/T	0.8362	likely_pathogenic	0.8356	pathogenic	-2.86	Highly Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
L/V	0.1663	likely_benign	0.1451	benign	-1.656	Destabilizing	0.999	D	0.491	neutral	N	0.490049768	None	None	N
L/W	0.9824	likely_pathogenic	0.9823	pathogenic	-2.072	Highly Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
L/Y	0.9824	likely_pathogenic	0.982	pathogenic	-1.804	Destabilizing	1.0	D	0.753	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.