TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3008	9247;9248;9249	chr2:178768814;178768813;178768812	chr2:179633541;179633540;179633539
N2AB	3008	9247;9248;9249	chr2:178768814;178768813;178768812	chr2:179633541;179633540;179633539
N2A	3008	9247;9248;9249	chr2:178768814;178768813;178768812	chr2:179633541;179633540;179633539
N2B	2962	9109;9110;9111	chr2:178768814;178768813;178768812	chr2:179633541;179633540;179633539
Novex-1	2962	9109;9110;9111	chr2:178768814;178768813;178768812	chr2:179633541;179633540;179633539
Novex-2	2962	9109;9110;9111	chr2:178768814;178768813;178768812	chr2:179633541;179633540;179633539
Novex-3	3008	9247;9248;9249	chr2:178768814;178768813;178768812	chr2:179633541;179633540;179633539

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-20
• Domain position: 40
• Structural Position: 58
• Q(SASA): 0.1198
• 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/V	rs756415356	-1.229	0.219	N	0.202	0.233	0.553793491129	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.8E-06	0
I/V	rs756415356	-1.229	0.219	N	0.202	0.233	0.553793491129	gnomAD-4.0.0	1.59061E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85647E-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	0.9833	likely_pathogenic	0.9842	pathogenic	-2.002	Highly Destabilizing	0.964	D	0.562	neutral	None	None	None	None	N
I/C	0.9876	likely_pathogenic	0.9887	pathogenic	-1.16	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
I/D	0.9992	likely_pathogenic	0.9992	pathogenic	-1.738	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
I/E	0.9937	likely_pathogenic	0.9943	pathogenic	-1.631	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
I/F	0.7803	likely_pathogenic	0.7867	pathogenic	-1.24	Destabilizing	0.997	D	0.56	neutral	D	0.683277771	None	None	N
I/G	0.9962	likely_pathogenic	0.9963	pathogenic	-2.429	Highly Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	N
I/H	0.9956	likely_pathogenic	0.9958	pathogenic	-1.651	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
I/K	0.9864	likely_pathogenic	0.9876	pathogenic	-1.508	Destabilizing	0.999	D	0.72	prob.delet.	None	None	None	None	N
I/L	0.3895	ambiguous	0.339	benign	-0.838	Destabilizing	0.817	D	0.369	neutral	N	0.498966124	None	None	N
I/M	0.3452	ambiguous	0.353	ambiguous	-0.629	Destabilizing	0.997	D	0.601	neutral	D	0.603219916	None	None	N
I/N	0.9841	likely_pathogenic	0.9846	pathogenic	-1.525	Destabilizing	0.999	D	0.755	deleterious	D	0.684769548	None	None	N
I/P	0.9981	likely_pathogenic	0.9978	pathogenic	-1.199	Destabilizing	0.999	D	0.756	deleterious	None	None	None	None	N
I/Q	0.9893	likely_pathogenic	0.9896	pathogenic	-1.561	Destabilizing	0.999	D	0.76	deleterious	None	None	None	None	N
I/R	0.9827	likely_pathogenic	0.984	pathogenic	-1.014	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
I/S	0.9903	likely_pathogenic	0.9905	pathogenic	-2.171	Highly Destabilizing	0.997	D	0.659	neutral	D	0.683905057	None	None	N
I/T	0.9728	likely_pathogenic	0.9771	pathogenic	-1.93	Destabilizing	0.98	D	0.583	neutral	D	0.639216869	None	None	N
I/V	0.2363	likely_benign	0.2428	benign	-1.199	Destabilizing	0.219	N	0.202	neutral	N	0.511759284	None	None	N
I/W	0.9915	likely_pathogenic	0.9925	pathogenic	-1.454	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
I/Y	0.974	likely_pathogenic	0.9742	pathogenic	-1.191	Destabilizing	0.999	D	0.709	prob.delet.	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.