TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18367	55324;55325;55326	chr2:178602303;178602302;178602301	chr2:179467030;179467029;179467028
N2AB	16726	50401;50402;50403	chr2:178602303;178602302;178602301	chr2:179467030;179467029;179467028
N2A	15799	47620;47621;47622	chr2:178602303;178602302;178602301	chr2:179467030;179467029;179467028
N2B	9302	28129;28130;28131	chr2:178602303;178602302;178602301	chr2:179467030;179467029;179467028
Novex-1	9427	28504;28505;28506	chr2:178602303;178602302;178602301	chr2:179467030;179467029;179467028
Novex-2	9494	28705;28706;28707	chr2:178602303;178602302;178602301	chr2:179467030;179467029;179467028
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-21
• Domain position: 96
• Structural Position: 127
• Q(SASA): 0.1112
• 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/S	rs758176369	None	0.988	N	0.765	0.463	0.875962154476	gnomAD-4.0.0	1.59366E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86225E-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	0.6762	likely_pathogenic	0.7792	pathogenic	-2.254	Highly Destabilizing	0.862	D	0.666	prob.neutral	None	None	None	None	N
I/C	0.7066	likely_pathogenic	0.7911	pathogenic	-1.43	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
I/D	0.8793	likely_pathogenic	0.9417	pathogenic	-2.347	Highly Destabilizing	0.997	D	0.853	deleterious	None	None	None	None	N
I/E	0.736	likely_pathogenic	0.8396	pathogenic	-2.125	Highly Destabilizing	0.997	D	0.829	deleterious	None	None	None	None	N
I/F	0.1645	likely_benign	0.2202	benign	-1.33	Destabilizing	0.988	D	0.739	deleterious	N	0.484438562	None	None	N
I/G	0.8785	likely_pathogenic	0.9319	pathogenic	-2.777	Highly Destabilizing	0.997	D	0.793	deleterious	None	None	None	None	N
I/H	0.5968	likely_pathogenic	0.7171	pathogenic	-2.053	Highly Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
I/K	0.5836	likely_pathogenic	0.6973	pathogenic	-1.742	Destabilizing	0.997	D	0.831	deleterious	None	None	None	None	N
I/L	0.1588	likely_benign	0.177	benign	-0.755	Destabilizing	0.506	D	0.392	neutral	N	0.503461782	None	None	N
I/M	0.1364	likely_benign	0.1582	benign	-0.625	Destabilizing	0.988	D	0.748	deleterious	N	0.496048357	None	None	N
I/N	0.4088	ambiguous	0.5201	ambiguous	-2.096	Highly Destabilizing	0.996	D	0.835	deleterious	N	0.497062315	None	None	N
I/P	0.9682	likely_pathogenic	0.9835	pathogenic	-1.235	Destabilizing	0.997	D	0.849	deleterious	None	None	None	None	N
I/Q	0.6166	likely_pathogenic	0.7219	pathogenic	-1.958	Destabilizing	0.997	D	0.817	deleterious	None	None	None	None	N
I/R	0.5537	ambiguous	0.6932	pathogenic	-1.469	Destabilizing	0.997	D	0.829	deleterious	None	None	None	None	N
I/S	0.5712	likely_pathogenic	0.6893	pathogenic	-2.785	Highly Destabilizing	0.988	D	0.765	deleterious	N	0.496555336	None	None	N
I/T	0.427	ambiguous	0.5183	ambiguous	-2.41	Highly Destabilizing	0.919	D	0.743	deleterious	N	0.484692052	None	None	N
I/V	0.1097	likely_benign	0.121	benign	-1.235	Destabilizing	0.06	N	0.184	neutral	N	0.412821135	None	None	N
I/W	0.7894	likely_pathogenic	0.8697	pathogenic	-1.65	Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
I/Y	0.4803	ambiguous	0.5791	pathogenic	-1.329	Destabilizing	0.997	D	0.817	deleterious	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.