TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35742	107449;107450;107451	chr2:178528427;178528426;178528425	chr2:179393154;179393153;179393152
N2AB	34101	102526;102527;102528	chr2:178528427;178528426;178528425	chr2:179393154;179393153;179393152
N2A	33174	99745;99746;99747	chr2:178528427;178528426;178528425	chr2:179393154;179393153;179393152
N2B	26677	80254;80255;80256	chr2:178528427;178528426;178528425	chr2:179393154;179393153;179393152
Novex-1	26802	80629;80630;80631	chr2:178528427;178528426;178528425	chr2:179393154;179393153;179393152
Novex-2	26869	80830;80831;80832	chr2:178528427;178528426;178528425	chr2:179393154;179393153;179393152
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: Ig-168
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.2067
• 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
I/F	None	None	0.982	N	0.55	0.552	0.46682414995	gnomAD-4.0.0	1.60034E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86535E-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
I/A	0.7602	likely_pathogenic	0.71	pathogenic	-1.844	Destabilizing	0.91	D	0.477	neutral	None	None	None	None	I
I/C	0.928	likely_pathogenic	0.9158	pathogenic	-1.21	Destabilizing	0.999	D	0.632	neutral	None	None	None	None	I
I/D	0.9865	likely_pathogenic	0.9798	pathogenic	-1.394	Destabilizing	0.998	D	0.768	deleterious	None	None	None	None	I
I/E	0.9708	likely_pathogenic	0.9577	pathogenic	-1.207	Destabilizing	0.993	D	0.749	deleterious	None	None	None	None	I
I/F	0.4016	ambiguous	0.347	ambiguous	-1.008	Destabilizing	0.982	D	0.55	neutral	N	0.499498759	None	None	I
I/G	0.9622	likely_pathogenic	0.9502	pathogenic	-2.315	Highly Destabilizing	0.993	D	0.739	prob.delet.	None	None	None	None	I
I/H	0.9599	likely_pathogenic	0.943	pathogenic	-1.506	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	I
I/K	0.9465	likely_pathogenic	0.9254	pathogenic	-1.273	Destabilizing	0.993	D	0.753	deleterious	None	None	None	None	I
I/L	0.1524	likely_benign	0.1367	benign	-0.526	Destabilizing	0.58	D	0.46	neutral	N	0.440586526	None	None	I
I/M	0.2361	likely_benign	0.217	benign	-0.564	Destabilizing	0.991	D	0.559	neutral	N	0.48772438	None	None	I
I/N	0.8961	likely_pathogenic	0.8542	pathogenic	-1.537	Destabilizing	0.997	D	0.779	deleterious	D	0.536721228	None	None	I
I/P	0.967	likely_pathogenic	0.9548	pathogenic	-0.942	Destabilizing	0.998	D	0.776	deleterious	None	None	None	None	I
I/Q	0.9437	likely_pathogenic	0.9223	pathogenic	-1.399	Destabilizing	0.998	D	0.774	deleterious	None	None	None	None	I
I/R	0.914	likely_pathogenic	0.8801	pathogenic	-1.062	Destabilizing	0.993	D	0.779	deleterious	None	None	None	None	I
I/S	0.8598	likely_pathogenic	0.8186	pathogenic	-2.257	Highly Destabilizing	0.991	D	0.655	neutral	N	0.521072508	None	None	I
I/T	0.7782	likely_pathogenic	0.742	pathogenic	-1.914	Destabilizing	0.939	D	0.549	neutral	N	0.521904974	None	None	I
I/V	0.0833	likely_benign	0.0786	benign	-0.942	Destabilizing	0.02	N	0.247	neutral	N	0.488268617	None	None	I
I/W	0.9744	likely_pathogenic	0.968	pathogenic	-1.22	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	I
I/Y	0.8925	likely_pathogenic	0.8662	pathogenic	-0.919	Destabilizing	0.993	D	0.651	neutral	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.