TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21675	65248;65249;65250	chr2:178584528;178584527;178584526	chr2:179449255;179449254;179449253
N2AB	20034	60325;60326;60327	chr2:178584528;178584527;178584526	chr2:179449255;179449254;179449253
N2A	19107	57544;57545;57546	chr2:178584528;178584527;178584526	chr2:179449255;179449254;179449253
N2B	12610	38053;38054;38055	chr2:178584528;178584527;178584526	chr2:179449255;179449254;179449253
Novex-1	12735	38428;38429;38430	chr2:178584528;178584527;178584526	chr2:179449255;179449254;179449253
Novex-2	12802	38629;38630;38631	chr2:178584528;178584527;178584526	chr2:179449255;179449254;179449253
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Fn3-45
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.1824
• 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
C/S	None	None	0.028	N	0.257	0.33	0.413635276047	gnomAD-4.0.0	1.59268E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8603E-06	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
C/A	0.4138	ambiguous	0.408	ambiguous	-1.711	Destabilizing	0.206	N	0.332	neutral	None	None	None	None	N
C/D	0.8277	likely_pathogenic	0.8187	pathogenic	-1.312	Destabilizing	0.742	D	0.63	neutral	None	None	None	None	N
C/E	0.8749	likely_pathogenic	0.8715	pathogenic	-1.152	Destabilizing	0.91	D	0.661	neutral	None	None	None	None	N
C/F	0.3114	likely_benign	0.3179	benign	-1.192	Destabilizing	0.003	N	0.365	neutral	N	0.425261996	None	None	N
C/G	0.2416	likely_benign	0.2294	benign	-2.038	Highly Destabilizing	0.521	D	0.543	neutral	N	0.455718189	None	None	N
C/H	0.5194	ambiguous	0.5014	ambiguous	-2.3	Highly Destabilizing	0.984	D	0.673	neutral	None	None	None	None	N
C/I	0.6129	likely_pathogenic	0.6418	pathogenic	-0.858	Destabilizing	0.742	D	0.515	neutral	None	None	None	None	N
C/K	0.8628	likely_pathogenic	0.8753	pathogenic	-1.252	Destabilizing	0.742	D	0.627	neutral	None	None	None	None	N
C/L	0.5769	likely_pathogenic	0.5843	pathogenic	-0.858	Destabilizing	0.373	N	0.395	neutral	None	None	None	None	N
C/M	0.6041	likely_pathogenic	0.6145	pathogenic	0.004	Stabilizing	0.984	D	0.641	neutral	None	None	None	None	N
C/N	0.4695	ambiguous	0.4425	ambiguous	-1.531	Destabilizing	0.91	D	0.675	prob.neutral	None	None	None	None	N
C/P	0.9961	likely_pathogenic	0.9965	pathogenic	-1.118	Destabilizing	0.953	D	0.676	prob.neutral	None	None	None	None	N
C/Q	0.6492	likely_pathogenic	0.6433	pathogenic	-1.31	Destabilizing	0.91	D	0.675	prob.neutral	None	None	None	None	N
C/R	0.5491	ambiguous	0.5517	ambiguous	-1.35	Destabilizing	0.884	D	0.677	prob.neutral	N	0.459681214	None	None	N
C/S	0.2468	likely_benign	0.2382	benign	-1.916	Destabilizing	0.028	N	0.257	neutral	N	0.340077523	None	None	N
C/T	0.3819	ambiguous	0.3798	ambiguous	-1.578	Destabilizing	0.59	D	0.501	neutral	None	None	None	None	N
C/V	0.4853	ambiguous	0.5033	ambiguous	-1.118	Destabilizing	0.742	D	0.505	neutral	None	None	None	None	N
C/W	0.6692	likely_pathogenic	0.6466	pathogenic	-1.434	Destabilizing	0.994	D	0.635	neutral	N	0.472573154	None	None	N
C/Y	0.3646	ambiguous	0.3608	ambiguous	-1.284	Destabilizing	0.521	D	0.574	neutral	N	0.445578554	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.