TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2860	8803;8804;8805	chr2:178770123;178770122;178770121	chr2:179634850;179634849;179634848
N2AB	2860	8803;8804;8805	chr2:178770123;178770122;178770121	chr2:179634850;179634849;179634848
N2A	2860	8803;8804;8805	chr2:178770123;178770122;178770121	chr2:179634850;179634849;179634848
N2B	2814	8665;8666;8667	chr2:178770123;178770122;178770121	chr2:179634850;179634849;179634848
Novex-1	2814	8665;8666;8667	chr2:178770123;178770122;178770121	chr2:179634850;179634849;179634848
Novex-2	2814	8665;8666;8667	chr2:178770123;178770122;178770121	chr2:179634850;179634849;179634848
Novex-3	2860	8803;8804;8805	chr2:178770123;178770122;178770121	chr2:179634850;179634849;179634848

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-18
• Domain position: 66
• Structural Position: 149
• Q(SASA): 0.1473
• 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
D/H	rs2091257509	None	0.994	D	0.801	0.559	0.663786076597	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	4.78927E-04
D/H	rs2091257509	None	0.994	D	0.801	0.559	0.663786076597	gnomAD-4.0.0	3.04486E-06	None	None	None	None	N	None	0	6.15082E-05	None	0	0	None	0	0	1.20494E-06	0	3.40298E-05

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
D/A	0.8231	likely_pathogenic	0.8227	pathogenic	0.155	Stabilizing	0.925	D	0.774	deleterious	D	0.726863293	None	None	N
D/C	0.9452	likely_pathogenic	0.9467	pathogenic	0.091	Stabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
D/E	0.6994	likely_pathogenic	0.7332	pathogenic	-0.756	Destabilizing	0.91	D	0.703	prob.neutral	D	0.690904337	None	None	N
D/F	0.9704	likely_pathogenic	0.9705	pathogenic	0.739	Stabilizing	0.999	D	0.859	deleterious	None	None	None	None	N
D/G	0.9132	likely_pathogenic	0.9107	pathogenic	-0.301	Destabilizing	0.91	D	0.749	deleterious	D	0.726121509	None	None	N
D/H	0.7958	likely_pathogenic	0.8118	pathogenic	0.213	Stabilizing	0.994	D	0.801	deleterious	D	0.667929675	None	None	N
D/I	0.9625	likely_pathogenic	0.9627	pathogenic	1.382	Stabilizing	0.996	D	0.873	deleterious	None	None	None	None	N
D/K	0.9658	likely_pathogenic	0.9669	pathogenic	-0.265	Destabilizing	0.97	D	0.779	deleterious	None	None	None	None	N
D/L	0.9511	likely_pathogenic	0.953	pathogenic	1.382	Stabilizing	0.996	D	0.849	deleterious	None	None	None	None	N
D/M	0.9657	likely_pathogenic	0.9647	pathogenic	1.827	Stabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
D/N	0.5206	ambiguous	0.564	ambiguous	-0.927	Destabilizing	0.122	N	0.349	neutral	D	0.608729815	None	None	N
D/P	0.9979	likely_pathogenic	0.9973	pathogenic	1.003	Stabilizing	0.996	D	0.826	deleterious	None	None	None	None	N
D/Q	0.8978	likely_pathogenic	0.9094	pathogenic	-0.58	Destabilizing	0.996	D	0.772	deleterious	None	None	None	None	N
D/R	0.9702	likely_pathogenic	0.9709	pathogenic	-0.245	Destabilizing	0.996	D	0.865	deleterious	None	None	None	None	N
D/S	0.6852	likely_pathogenic	0.6859	pathogenic	-1.209	Destabilizing	0.559	D	0.405	neutral	None	None	None	None	N
D/T	0.9228	likely_pathogenic	0.9244	pathogenic	-0.804	Destabilizing	0.942	D	0.753	deleterious	None	None	None	None	N
D/V	0.8907	likely_pathogenic	0.8942	pathogenic	1.003	Stabilizing	0.994	D	0.863	deleterious	D	0.726124677	None	None	N
D/W	0.9953	likely_pathogenic	0.9952	pathogenic	0.732	Stabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
D/Y	0.8449	likely_pathogenic	0.8412	pathogenic	0.944	Stabilizing	0.998	D	0.861	deleterious	D	0.689301729	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.