TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31180	93763;93764;93765	chr2:178548088;178548087;178548086	chr2:179412815;179412814;179412813
N2AB	29539	88840;88841;88842	chr2:178548088;178548087;178548086	chr2:179412815;179412814;179412813
N2A	28612	86059;86060;86061	chr2:178548088;178548087;178548086	chr2:179412815;179412814;179412813
N2B	22115	66568;66569;66570	chr2:178548088;178548087;178548086	chr2:179412815;179412814;179412813
Novex-1	22240	66943;66944;66945	chr2:178548088;178548087;178548086	chr2:179412815;179412814;179412813
Novex-2	22307	67144;67145;67146	chr2:178548088;178548087;178548086	chr2:179412815;179412814;179412813
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-115
• Domain position: 68
• Structural Position: 102
• Q(SASA): 0.1451
• 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
T/S	None	None	0.659	N	0.299	0.16	0.186928172975	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
T/A	0.0816	likely_benign	0.0798	benign	-0.792	Destabilizing	0.911	D	0.453	neutral	N	0.423864848	None	None	N
T/C	0.3713	ambiguous	0.4125	ambiguous	-0.499	Destabilizing	1.0	D	0.514	neutral	None	None	None	None	N
T/D	0.3802	ambiguous	0.3584	ambiguous	-0.502	Destabilizing	0.985	D	0.495	neutral	None	None	None	None	N
T/E	0.2282	likely_benign	0.2077	benign	-0.362	Destabilizing	0.985	D	0.489	neutral	None	None	None	None	N
T/F	0.3224	likely_benign	0.3477	ambiguous	-0.526	Destabilizing	0.999	D	0.557	neutral	None	None	None	None	N
T/G	0.2477	likely_benign	0.2405	benign	-1.169	Destabilizing	0.985	D	0.501	neutral	None	None	None	None	N
T/H	0.2639	likely_benign	0.2755	benign	-1.259	Destabilizing	1.0	D	0.549	neutral	None	None	None	None	N
T/I	0.2288	likely_benign	0.2435	benign	0.166	Stabilizing	0.997	D	0.539	neutral	N	0.495997092	None	None	N
T/K	0.1988	likely_benign	0.1748	benign	-0.461	Destabilizing	0.469	N	0.333	neutral	None	None	None	None	N
T/L	0.1371	likely_benign	0.1401	benign	0.166	Stabilizing	0.993	D	0.485	neutral	None	None	None	None	N
T/M	0.0851	likely_benign	0.0872	benign	0.084	Stabilizing	1.0	D	0.518	neutral	None	None	None	None	N
T/N	0.1212	likely_benign	0.1208	benign	-0.889	Destabilizing	0.98	D	0.495	neutral	N	0.485953457	None	None	N
T/P	0.7248	likely_pathogenic	0.6421	pathogenic	-0.12	Destabilizing	0.997	D	0.545	neutral	N	0.497980006	None	None	N
T/Q	0.1793	likely_benign	0.1743	benign	-0.741	Destabilizing	0.996	D	0.554	neutral	None	None	None	None	N
T/R	0.1749	likely_benign	0.1481	benign	-0.532	Destabilizing	0.323	N	0.344	neutral	None	None	None	None	N
T/S	0.1044	likely_benign	0.1063	benign	-1.168	Destabilizing	0.659	D	0.299	neutral	N	0.431233537	None	None	N
T/V	0.1553	likely_benign	0.1653	benign	-0.12	Destabilizing	0.993	D	0.511	neutral	None	None	None	None	N
T/W	0.6285	likely_pathogenic	0.6193	pathogenic	-0.63	Destabilizing	1.0	D	0.564	neutral	None	None	None	None	N
T/Y	0.3099	likely_benign	0.3224	benign	-0.272	Destabilizing	0.999	D	0.561	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.