TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33294	100105;100106;100107	chr2:178537229;178537228;178537227	chr2:179401956;179401955;179401954
N2AB	31653	95182;95183;95184	chr2:178537229;178537228;178537227	chr2:179401956;179401955;179401954
N2A	30726	92401;92402;92403	chr2:178537229;178537228;178537227	chr2:179401956;179401955;179401954
N2B	24229	72910;72911;72912	chr2:178537229;178537228;178537227	chr2:179401956;179401955;179401954
Novex-1	24354	73285;73286;73287	chr2:178537229;178537228;178537227	chr2:179401956;179401955;179401954
Novex-2	24421	73486;73487;73488	chr2:178537229;178537228;178537227	chr2:179401956;179401955;179401954
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-130
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.2236
• 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/S	None	None	1.0	D	0.895	0.725	0.695033247173	gnomAD-4.0.0	6.92161E-07	None	None	None	None	I	None	0	0	None	0	2.5391E-05	None	0	0	0	0	0
P/T	None	None	1.0	D	0.881	0.742	0.833527091442	gnomAD-4.0.0	6.92161E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.08039E-07	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	0.8166	likely_pathogenic	0.8606	pathogenic	-2.365	Highly Destabilizing	1.0	D	0.851	deleterious	D	0.611371233	None	None	I
P/C	0.9745	likely_pathogenic	0.9832	pathogenic	-2.485	Highly Destabilizing	1.0	D	0.935	deleterious	None	None	None	None	I
P/D	0.9987	likely_pathogenic	0.9987	pathogenic	-3.587	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	I
P/E	0.9967	likely_pathogenic	0.9964	pathogenic	-3.397	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	I
P/F	0.9979	likely_pathogenic	0.9983	pathogenic	-1.382	Destabilizing	1.0	D	0.946	deleterious	None	None	None	None	I
P/G	0.9885	likely_pathogenic	0.991	pathogenic	-2.844	Highly Destabilizing	1.0	D	0.934	deleterious	None	None	None	None	I
P/H	0.997	likely_pathogenic	0.997	pathogenic	-2.394	Highly Destabilizing	1.0	D	0.913	deleterious	D	0.649355155	None	None	I
P/I	0.9218	likely_pathogenic	0.9427	pathogenic	-1.025	Destabilizing	1.0	D	0.952	deleterious	None	None	None	None	I
P/K	0.9981	likely_pathogenic	0.998	pathogenic	-2.067	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	I
P/L	0.8677	likely_pathogenic	0.8955	pathogenic	-1.025	Destabilizing	1.0	D	0.937	deleterious	D	0.648951547	None	None	I
P/M	0.9756	likely_pathogenic	0.9793	pathogenic	-1.39	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	I
P/N	0.9975	likely_pathogenic	0.9973	pathogenic	-2.502	Highly Destabilizing	1.0	D	0.959	deleterious	None	None	None	None	I
P/Q	0.9943	likely_pathogenic	0.9941	pathogenic	-2.406	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	I
P/R	0.9948	likely_pathogenic	0.9943	pathogenic	-1.768	Destabilizing	1.0	D	0.961	deleterious	D	0.649153351	None	None	I
P/S	0.9873	likely_pathogenic	0.9898	pathogenic	-3.014	Highly Destabilizing	1.0	D	0.895	deleterious	D	0.623413435	None	None	I
P/T	0.9577	likely_pathogenic	0.9655	pathogenic	-2.695	Highly Destabilizing	1.0	D	0.881	deleterious	D	0.623615239	None	None	I
P/V	0.8262	likely_pathogenic	0.8763	pathogenic	-1.449	Destabilizing	1.0	D	0.939	deleterious	None	None	None	None	I
P/W	0.9997	likely_pathogenic	0.9998	pathogenic	-1.858	Destabilizing	1.0	D	0.936	deleterious	None	None	None	None	I
P/Y	0.9991	likely_pathogenic	0.9991	pathogenic	-1.584	Destabilizing	1.0	D	0.957	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.