TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6988	21187;21188;21189	chr2:178724413;178724412;178724411	chr2:179589140;179589139;179589138
N2AB	6671	20236;20237;20238	chr2:178724413;178724412;178724411	chr2:179589140;179589139;179589138
N2A	5744	17455;17456;17457	chr2:178724413;178724412;178724411	chr2:179589140;179589139;179589138
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-54
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.1932
• 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/S	rs1159385830	None	1.0	D	0.806	0.745	0.889413966974	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	1.47E-05	0	0
L/S	rs1159385830	None	1.0	D	0.806	0.745	0.889413966974	gnomAD-4.0.0	2.62905E-05	None	None	None	None	N	None	7.23554E-05	0	None	0	0	None	0	0	1.4708E-05	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	0.8654	likely_pathogenic	0.8456	pathogenic	-2.042	Highly Destabilizing	0.998	D	0.621	neutral	None	None	None	None	N
L/C	0.9083	likely_pathogenic	0.881	pathogenic	-1.169	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
L/D	0.9934	likely_pathogenic	0.9932	pathogenic	-2.156	Highly Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
L/E	0.9349	likely_pathogenic	0.9315	pathogenic	-1.917	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
L/F	0.5111	ambiguous	0.4829	ambiguous	-1.271	Destabilizing	0.999	D	0.736	prob.delet.	N	0.50736648	None	None	N
L/G	0.9744	likely_pathogenic	0.9723	pathogenic	-2.54	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
L/H	0.87	likely_pathogenic	0.8665	pathogenic	-1.872	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
L/I	0.142	likely_benign	0.1287	benign	-0.602	Destabilizing	0.91	D	0.366	neutral	None	None	None	None	N
L/K	0.9011	likely_pathogenic	0.8922	pathogenic	-1.388	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
L/M	0.2833	likely_benign	0.2578	benign	-0.539	Destabilizing	0.999	D	0.767	deleterious	N	0.502175467	None	None	N
L/N	0.9705	likely_pathogenic	0.9697	pathogenic	-1.82	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
L/P	0.9659	likely_pathogenic	0.968	pathogenic	-1.065	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
L/Q	0.7545	likely_pathogenic	0.7387	pathogenic	-1.629	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
L/R	0.8246	likely_pathogenic	0.8012	pathogenic	-1.302	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
L/S	0.9592	likely_pathogenic	0.9543	pathogenic	-2.468	Highly Destabilizing	1.0	D	0.806	deleterious	D	0.536093025	None	None	N
L/T	0.8965	likely_pathogenic	0.8826	pathogenic	-2.074	Highly Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
L/V	0.1988	likely_benign	0.164	benign	-1.065	Destabilizing	0.981	D	0.526	neutral	N	0.499816549	None	None	N
L/W	0.8101	likely_pathogenic	0.7895	pathogenic	-1.554	Destabilizing	1.0	D	0.805	deleterious	D	0.543854933	None	None	N
L/Y	0.875	likely_pathogenic	0.8675	pathogenic	-1.216	Destabilizing	1.0	D	0.814	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.