TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32128	96607;96608;96609	chr2:178543591;178543590;178543589	chr2:179408318;179408317;179408316
N2AB	30487	91684;91685;91686	chr2:178543591;178543590;178543589	chr2:179408318;179408317;179408316
N2A	29560	88903;88904;88905	chr2:178543591;178543590;178543589	chr2:179408318;179408317;179408316
N2B	23063	69412;69413;69414	chr2:178543591;178543590;178543589	chr2:179408318;179408317;179408316
Novex-1	23188	69787;69788;69789	chr2:178543591;178543590;178543589	chr2:179408318;179408317;179408316
Novex-2	23255	69988;69989;69990	chr2:178543591;178543590;178543589	chr2:179408318;179408317;179408316
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-122
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.4299
• 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
I/T	None	None	0.002	N	0.288	0.149	0.458013479912	gnomAD-4.0.0	1.60769E-06	None	None	None	None	N	None	0	0	None	0	0	None	2.12558E-05	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
I/A	0.2262	likely_benign	0.2336	benign	-1.654	Destabilizing	0.035	N	0.392	neutral	None	None	None	None	N
I/C	0.5669	likely_pathogenic	0.5769	pathogenic	-0.96	Destabilizing	0.824	D	0.561	neutral	None	None	None	None	N
I/D	0.581	likely_pathogenic	0.5849	pathogenic	-1.647	Destabilizing	0.38	N	0.621	neutral	None	None	None	None	N
I/E	0.4765	ambiguous	0.5039	ambiguous	-1.615	Destabilizing	0.38	N	0.606	neutral	None	None	None	None	N
I/F	0.1727	likely_benign	0.1629	benign	-1.15	Destabilizing	0.317	N	0.513	neutral	N	0.444522548	None	None	N
I/G	0.5031	ambiguous	0.4966	ambiguous	-1.965	Destabilizing	0.149	N	0.593	neutral	None	None	None	None	N
I/H	0.4586	ambiguous	0.47	ambiguous	-1.103	Destabilizing	0.935	D	0.593	neutral	None	None	None	None	N
I/K	0.3265	likely_benign	0.3318	benign	-1.277	Destabilizing	0.38	N	0.612	neutral	None	None	None	None	N
I/L	0.0986	likely_benign	0.0991	benign	-0.85	Destabilizing	0.012	N	0.308	neutral	N	0.409716541	None	None	N
I/M	0.082	likely_benign	0.0818	benign	-0.765	Destabilizing	0.317	N	0.513	neutral	N	0.407081667	None	None	N
I/N	0.1951	likely_benign	0.1942	benign	-1.16	Destabilizing	0.317	N	0.6	neutral	N	0.444002473	None	None	N
I/P	0.2736	likely_benign	0.2961	benign	-1.091	Destabilizing	0.555	D	0.599	neutral	None	None	None	None	N
I/Q	0.3468	ambiguous	0.3635	ambiguous	-1.313	Destabilizing	0.555	D	0.607	neutral	None	None	None	None	N
I/R	0.315	likely_benign	0.3121	benign	-0.673	Destabilizing	0.555	D	0.603	neutral	None	None	None	None	N
I/S	0.2135	likely_benign	0.216	benign	-1.626	Destabilizing	0.062	N	0.506	neutral	N	0.377316121	None	None	N
I/T	0.1801	likely_benign	0.1916	benign	-1.48	Destabilizing	0.002	N	0.288	neutral	N	0.381529862	None	None	N
I/V	0.0724	likely_benign	0.072	benign	-1.091	Destabilizing	None	N	0.117	neutral	N	0.372545019	None	None	N
I/W	0.7666	likely_pathogenic	0.7537	pathogenic	-1.243	Destabilizing	0.935	D	0.641	neutral	None	None	None	None	N
I/Y	0.4436	ambiguous	0.4231	ambiguous	-1.028	Destabilizing	0.555	D	0.579	neutral	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.