TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8259	25000;25001;25002	chr2:178718331;178718330;178718329	chr2:179583058;179583057;179583056
N2AB	7942	24049;24050;24051	chr2:178718331;178718330;178718329	chr2:179583058;179583057;179583056
N2A	7015	21268;21269;21270	chr2:178718331;178718330;178718329	chr2:179583058;179583057;179583056
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: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-67
• Domain position: 89
• Structural Position: 175
• Q(SASA): 0.2025
• 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
S/F	None	None	0.457	N	0.473	0.307	0.521070178209	gnomAD-4.0.0	6.84578E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99881E-07	0	0
S/Y	rs868000266	None	0.001	N	0.404	0.309	0.481543764896	gnomAD-4.0.0	8.89951E-06	None	None	None	None	N	None	2.99168E-05	0	None	0	0	None	0	2.08551E-03	0	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
S/A	0.1025	likely_benign	0.1105	benign	-0.57	Destabilizing	0.079	N	0.362	neutral	N	0.494162253	None	None	N
S/C	0.2022	likely_benign	0.2468	benign	-0.209	Destabilizing	0.975	D	0.46	neutral	N	0.508306943	None	None	N
S/D	0.5596	ambiguous	0.6209	pathogenic	0.435	Stabilizing	0.563	D	0.42	neutral	None	None	None	None	N
S/E	0.5977	likely_pathogenic	0.6714	pathogenic	0.517	Stabilizing	0.563	D	0.372	neutral	None	None	None	None	N
S/F	0.2117	likely_benign	0.2576	benign	-0.583	Destabilizing	0.457	N	0.473	neutral	N	0.484922769	None	None	N
S/G	0.2125	likely_benign	0.2394	benign	-0.879	Destabilizing	0.563	D	0.371	neutral	None	None	None	None	N
S/H	0.3783	ambiguous	0.4384	ambiguous	-1.113	Destabilizing	0.69	D	0.485	neutral	None	None	None	None	N
S/I	0.306	likely_benign	0.35	ambiguous	0.166	Stabilizing	0.241	N	0.467	neutral	None	None	None	None	N
S/K	0.715	likely_pathogenic	0.7915	pathogenic	0.073	Stabilizing	0.388	N	0.375	neutral	None	None	None	None	N
S/L	0.1339	likely_benign	0.1449	benign	0.166	Stabilizing	0.116	N	0.444	neutral	None	None	None	None	N
S/M	0.2514	likely_benign	0.2746	benign	0.069	Stabilizing	0.818	D	0.487	neutral	None	None	None	None	N
S/N	0.2539	likely_benign	0.2867	benign	-0.121	Destabilizing	0.563	D	0.437	neutral	None	None	None	None	N
S/P	0.909	likely_pathogenic	0.9254	pathogenic	-0.045	Destabilizing	0.912	D	0.448	neutral	N	0.519156269	None	None	N
S/Q	0.5701	likely_pathogenic	0.6244	pathogenic	-0.072	Destabilizing	0.818	D	0.45	neutral	None	None	None	None	N
S/R	0.6334	likely_pathogenic	0.7119	pathogenic	-0.097	Destabilizing	0.818	D	0.45	neutral	None	None	None	None	N
S/T	0.0958	likely_benign	0.101	benign	-0.133	Destabilizing	0.006	N	0.129	neutral	N	0.454422615	None	None	N
S/V	0.2663	likely_benign	0.2945	benign	-0.045	Destabilizing	0.008	N	0.319	neutral	None	None	None	None	N
S/W	0.3733	ambiguous	0.4237	ambiguous	-0.615	Destabilizing	0.944	D	0.545	neutral	None	None	None	None	N
S/Y	0.1676	likely_benign	0.2068	benign	-0.25	Destabilizing	0.001	N	0.404	neutral	N	0.496697148	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.