TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18482	55669;55670;55671	chr2:178601553;178601552;178601551	chr2:179466280;179466279;179466278
N2AB	16841	50746;50747;50748	chr2:178601553;178601552;178601551	chr2:179466280;179466279;179466278
N2A	15914	47965;47966;47967	chr2:178601553;178601552;178601551	chr2:179466280;179466279;179466278
N2B	9417	28474;28475;28476	chr2:178601553;178601552;178601551	chr2:179466280;179466279;179466278
Novex-1	9542	28849;28850;28851	chr2:178601553;178601552;178601551	chr2:179466280;179466279;179466278
Novex-2	9609	29050;29051;29052	chr2:178601553;178601552;178601551	chr2:179466280;179466279;179466278
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-22
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.2776
• Predicted PPI site: I

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
P/L	None	None	0.998	N	0.829	0.484	0.65545073463	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	6.33473E-05	0	None	0	0	None	0	0	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
P/A	0.0795	likely_benign	0.0821	benign	-1.666	Destabilizing	0.619	D	0.379	neutral	N	0.467471191	None	None	I
P/C	0.5361	ambiguous	0.5267	ambiguous	-0.86	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	I
P/D	0.8516	likely_pathogenic	0.8517	pathogenic	-1.853	Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	I
P/E	0.5207	ambiguous	0.5042	ambiguous	-1.867	Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	I
P/F	0.6474	likely_pathogenic	0.6368	pathogenic	-1.318	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	I
P/G	0.5039	ambiguous	0.5461	ambiguous	-1.97	Destabilizing	0.988	D	0.782	deleterious	None	None	None	None	I
P/H	0.4251	ambiguous	0.4312	ambiguous	-1.589	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
P/I	0.4026	ambiguous	0.3876	ambiguous	-0.918	Destabilizing	0.999	D	0.86	deleterious	None	None	None	None	I
P/K	0.4638	ambiguous	0.4754	ambiguous	-1.448	Destabilizing	0.998	D	0.803	deleterious	None	None	None	None	I
P/L	0.2255	likely_benign	0.226	benign	-0.918	Destabilizing	0.998	D	0.829	deleterious	N	0.509987286	None	None	I
P/M	0.3841	ambiguous	0.3738	ambiguous	-0.554	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
P/N	0.6643	likely_pathogenic	0.6707	pathogenic	-1.14	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	I
P/Q	0.2586	likely_benign	0.2678	benign	-1.358	Destabilizing	1.0	D	0.829	deleterious	N	0.498996147	None	None	I
P/R	0.353	ambiguous	0.3736	ambiguous	-0.848	Destabilizing	0.999	D	0.863	deleterious	N	0.499503126	None	None	I
P/S	0.1985	likely_benign	0.2136	benign	-1.56	Destabilizing	0.984	D	0.751	deleterious	N	0.477182136	None	None	I
P/T	0.2292	likely_benign	0.2409	benign	-1.487	Destabilizing	0.998	D	0.807	deleterious	N	0.505859456	None	None	I
P/V	0.2871	likely_benign	0.2915	benign	-1.135	Destabilizing	0.998	D	0.831	deleterious	None	None	None	None	I
P/W	0.8661	likely_pathogenic	0.8624	pathogenic	-1.537	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
P/Y	0.6897	likely_pathogenic	0.683	pathogenic	-1.299	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	I

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.