TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24169	72730;72731;72732	chr2:178573627;178573626;178573625	chr2:179438354;179438353;179438352
N2AB	22528	67807;67808;67809	chr2:178573627;178573626;178573625	chr2:179438354;179438353;179438352
N2A	21601	65026;65027;65028	chr2:178573627;178573626;178573625	chr2:179438354;179438353;179438352
N2B	15104	45535;45536;45537	chr2:178573627;178573626;178573625	chr2:179438354;179438353;179438352
Novex-1	15229	45910;45911;45912	chr2:178573627;178573626;178573625	chr2:179438354;179438353;179438352
Novex-2	15296	46111;46112;46113	chr2:178573627;178573626;178573625	chr2:179438354;179438353;179438352
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-63
• Domain position: 48
• Structural Position: 64
• Q(SASA): 0.4775
• 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
A/T	None	None	0.067	N	0.339	0.127	0.392395365052	gnomAD-4.0.0	1.94048E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.36279E-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
A/C	0.5918	likely_pathogenic	0.7684	pathogenic	-0.63	Destabilizing	1.0	D	0.59	neutral	None	None	None	None	I
A/D	0.8758	likely_pathogenic	0.9497	pathogenic	-0.522	Destabilizing	0.991	D	0.658	neutral	None	None	None	None	I
A/E	0.7798	likely_pathogenic	0.9026	pathogenic	-0.617	Destabilizing	0.988	D	0.563	neutral	N	0.469858136	None	None	I
A/F	0.5932	likely_pathogenic	0.7198	pathogenic	-0.854	Destabilizing	0.995	D	0.689	prob.neutral	None	None	None	None	I
A/G	0.3249	likely_benign	0.458	ambiguous	-0.682	Destabilizing	0.958	D	0.457	neutral	N	0.475920103	None	None	I
A/H	0.8134	likely_pathogenic	0.8981	pathogenic	-0.696	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
A/I	0.3576	ambiguous	0.4934	ambiguous	-0.317	Destabilizing	0.991	D	0.586	neutral	None	None	None	None	I
A/K	0.928	likely_pathogenic	0.9694	pathogenic	-0.83	Destabilizing	0.991	D	0.569	neutral	None	None	None	None	I
A/L	0.2067	likely_benign	0.2816	benign	-0.317	Destabilizing	0.938	D	0.503	neutral	None	None	None	None	I
A/M	0.3399	likely_benign	0.4675	ambiguous	-0.388	Destabilizing	1.0	D	0.626	neutral	None	None	None	None	I
A/N	0.5198	ambiguous	0.6693	pathogenic	-0.464	Destabilizing	0.991	D	0.647	neutral	None	None	None	None	I
A/P	0.7459	likely_pathogenic	0.8481	pathogenic	-0.351	Destabilizing	0.994	D	0.564	neutral	N	0.515998644	None	None	I
A/Q	0.6521	likely_pathogenic	0.7818	pathogenic	-0.678	Destabilizing	0.995	D	0.603	neutral	None	None	None	None	I
A/R	0.8592	likely_pathogenic	0.9212	pathogenic	-0.41	Destabilizing	0.991	D	0.567	neutral	None	None	None	None	I
A/S	0.1474	likely_benign	0.1858	benign	-0.732	Destabilizing	0.919	D	0.449	neutral	N	0.442191532	None	None	I
A/T	0.14	likely_benign	0.2361	benign	-0.74	Destabilizing	0.067	N	0.339	neutral	N	0.428206301	None	None	I
A/V	0.1664	likely_benign	0.2427	benign	-0.351	Destabilizing	0.919	D	0.467	neutral	N	0.482502146	None	None	I
A/W	0.9336	likely_pathogenic	0.9656	pathogenic	-1.079	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
A/Y	0.7829	likely_pathogenic	0.8809	pathogenic	-0.707	Destabilizing	0.998	D	0.687	prob.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.