TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2915	8968;8969;8970	chr2:178769838;178769837;178769836	chr2:179634565;179634564;179634563
N2AB	2915	8968;8969;8970	chr2:178769838;178769837;178769836	chr2:179634565;179634564;179634563
N2A	2915	8968;8969;8970	chr2:178769838;178769837;178769836	chr2:179634565;179634564;179634563
N2B	2869	8830;8831;8832	chr2:178769838;178769837;178769836	chr2:179634565;179634564;179634563
Novex-1	2869	8830;8831;8832	chr2:178769838;178769837;178769836	chr2:179634565;179634564;179634563
Novex-2	2869	8830;8831;8832	chr2:178769838;178769837;178769836	chr2:179634565;179634564;179634563
Novex-3	2915	8968;8969;8970	chr2:178769838;178769837;178769836	chr2:179634565;179634564;179634563

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-19
• Domain position: 34
• Structural Position: 49
• Q(SASA): 0.1534
• 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/Q	None	None	1.0	D	0.743	0.764	0.847965046105	gnomAD-4.0.0	6.84065E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15931E-05	0
L/R	None	None	1.0	D	0.757	0.754	0.849054655723	gnomAD-4.0.0	6.84065E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99297E-07	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	0.8646	likely_pathogenic	0.8375	pathogenic	-2.237	Highly Destabilizing	0.999	D	0.646	neutral	None	None	None	None	N
L/C	0.8016	likely_pathogenic	0.807	pathogenic	-1.525	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
L/D	0.9891	likely_pathogenic	0.9842	pathogenic	-2.341	Highly Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
L/E	0.8325	likely_pathogenic	0.8026	pathogenic	-2.203	Highly Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
L/F	0.2854	likely_benign	0.2751	benign	-1.381	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	N
L/G	0.9567	likely_pathogenic	0.945	pathogenic	-2.699	Highly Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
L/H	0.5836	likely_pathogenic	0.5777	pathogenic	-2.082	Highly Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
L/I	0.2831	likely_benign	0.2399	benign	-0.948	Destabilizing	0.999	D	0.48	neutral	None	None	None	None	N
L/K	0.41	ambiguous	0.4418	ambiguous	-1.635	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
L/M	0.1846	likely_benign	0.1845	benign	-0.854	Destabilizing	1.0	D	0.675	neutral	D	0.523862085	None	None	N
L/N	0.9077	likely_pathogenic	0.8859	pathogenic	-1.753	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
L/P	0.9992	likely_pathogenic	0.9983	pathogenic	-1.354	Destabilizing	1.0	D	0.763	deleterious	D	0.701601165	None	None	N
L/Q	0.3735	ambiguous	0.3748	ambiguous	-1.76	Destabilizing	1.0	D	0.743	deleterious	D	0.58236	None	None	N
L/R	0.3644	ambiguous	0.3935	ambiguous	-1.205	Destabilizing	1.0	D	0.757	deleterious	D	0.567455978	None	None	N
L/S	0.8869	likely_pathogenic	0.8479	pathogenic	-2.421	Highly Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
L/T	0.7611	likely_pathogenic	0.7075	pathogenic	-2.156	Highly Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
L/V	0.278	likely_benign	0.2581	benign	-1.354	Destabilizing	0.999	D	0.513	neutral	D	0.579141422	None	None	N
L/W	0.5334	ambiguous	0.5307	ambiguous	-1.696	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
L/Y	0.5856	likely_pathogenic	0.5814	pathogenic	-1.415	Destabilizing	1.0	D	0.745	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.