TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3231	9916;9917;9918	chr2:178766393;178766392;178766391	chr2:179631120;179631119;179631118
N2AB	3231	9916;9917;9918	chr2:178766393;178766392;178766391	chr2:179631120;179631119;179631118
N2A	3231	9916;9917;9918	chr2:178766393;178766392;178766391	chr2:179631120;179631119;179631118
N2B	3185	9778;9779;9780	chr2:178766393;178766392;178766391	chr2:179631120;179631119;179631118
Novex-1	3185	9778;9779;9780	chr2:178766393;178766392;178766391	chr2:179631120;179631119;179631118
Novex-2	3185	9778;9779;9780	chr2:178766393;178766392;178766391	chr2:179631120;179631119;179631118
Novex-3	3231	9916;9917;9918	chr2:178766393;178766392;178766391	chr2:179631120;179631119;179631118

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-22
• Domain position: 85
• Structural Position: 174
• Q(SASA): 0.11
• 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
L/F	rs786205404	None	1.0	N	0.74	0.353	0.467839254973	gnomAD-4.0.0	1.37231E-06	None	None	None	None	N	None	0	2.23674E-05	None	0	0	None	0	0	0	0	1.66041E-05

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
L/A	0.9051	likely_pathogenic	0.9774	pathogenic	-2.67	Highly Destabilizing	0.999	D	0.664	neutral	None	None	None	None	N
L/C	0.928	likely_pathogenic	0.9703	pathogenic	-1.818	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
L/D	0.9988	likely_pathogenic	0.9998	pathogenic	-3.171	Highly Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
L/E	0.9927	likely_pathogenic	0.999	pathogenic	-2.885	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
L/F	0.715	likely_pathogenic	0.8871	pathogenic	-1.578	Destabilizing	1.0	D	0.74	deleterious	N	0.462644014	None	None	N
L/G	0.9883	likely_pathogenic	0.9974	pathogenic	-3.27	Highly Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
L/H	0.9775	likely_pathogenic	0.9977	pathogenic	-2.835	Highly Destabilizing	1.0	D	0.82	deleterious	N	0.466031929	None	None	N
L/I	0.2556	likely_benign	0.3093	benign	-0.897	Destabilizing	0.999	D	0.509	neutral	N	0.424485033	None	None	N
L/K	0.9841	likely_pathogenic	0.9981	pathogenic	-2.024	Highly Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
L/M	0.4091	ambiguous	0.6218	pathogenic	-0.878	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
L/N	0.9922	likely_pathogenic	0.9987	pathogenic	-2.562	Highly Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
L/P	0.9964	likely_pathogenic	0.9988	pathogenic	-1.474	Destabilizing	1.0	D	0.835	deleterious	N	0.466031929	None	None	N
L/Q	0.965	likely_pathogenic	0.9961	pathogenic	-2.308	Highly Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
L/R	0.9605	likely_pathogenic	0.9943	pathogenic	-1.901	Destabilizing	1.0	D	0.829	deleterious	N	0.465617395	None	None	N
L/S	0.9799	likely_pathogenic	0.9976	pathogenic	-3.224	Highly Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
L/T	0.9384	likely_pathogenic	0.9891	pathogenic	-2.779	Highly Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
L/V	0.2984	likely_benign	0.3946	ambiguous	-1.474	Destabilizing	0.999	D	0.51	neutral	N	0.382163518	None	None	N
L/W	0.9619	likely_pathogenic	0.994	pathogenic	-2.034	Highly Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
L/Y	0.9602	likely_pathogenic	0.9927	pathogenic	-1.741	Destabilizing	1.0	D	0.829	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.