TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32432	97519;97520;97521	chr2:178542462;178542461;178542460	chr2:179407189;179407188;179407187
N2AB	30791	92596;92597;92598	chr2:178542462;178542461;178542460	chr2:179407189;179407188;179407187
N2A	29864	89815;89816;89817	chr2:178542462;178542461;178542460	chr2:179407189;179407188;179407187
N2B	23367	70324;70325;70326	chr2:178542462;178542461;178542460	chr2:179407189;179407188;179407187
Novex-1	23492	70699;70700;70701	chr2:178542462;178542461;178542460	chr2:179407189;179407188;179407187
Novex-2	23559	70900;70901;70902	chr2:178542462;178542461;178542460	chr2:179407189;179407188;179407187
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-124
• Domain position: 34
• Structural Position: 35
• Q(SASA): 0.2622
• 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
L/P	rs1199606807	-1.481	0.995	N	0.813	0.418	0.799146553086	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.91E-06	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
L/A	0.651	likely_pathogenic	0.5725	pathogenic	-2.037	Highly Destabilizing	0.825	D	0.688	prob.neutral	None	None	None	None	I
L/C	0.713	likely_pathogenic	0.6681	pathogenic	-1.193	Destabilizing	0.999	D	0.738	prob.delet.	None	None	None	None	I
L/D	0.9798	likely_pathogenic	0.9696	pathogenic	-1.493	Destabilizing	0.996	D	0.815	deleterious	None	None	None	None	I
L/E	0.8785	likely_pathogenic	0.8413	pathogenic	-1.46	Destabilizing	0.996	D	0.809	deleterious	None	None	None	None	I
L/F	0.5296	ambiguous	0.4466	ambiguous	-1.493	Destabilizing	0.976	D	0.66	neutral	None	None	None	None	I
L/G	0.9258	likely_pathogenic	0.8941	pathogenic	-2.41	Highly Destabilizing	0.996	D	0.805	deleterious	None	None	None	None	I
L/H	0.7897	likely_pathogenic	0.7336	pathogenic	-1.61	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	I
L/I	0.0758	likely_benign	0.0741	benign	-1.059	Destabilizing	0.015	N	0.204	neutral	None	None	None	None	I
L/K	0.7931	likely_pathogenic	0.77	pathogenic	-1.341	Destabilizing	0.988	D	0.791	deleterious	None	None	None	None	I
L/M	0.2135	likely_benign	0.1957	benign	-0.736	Destabilizing	0.968	D	0.655	neutral	N	0.504186927	None	None	I
L/N	0.8457	likely_pathogenic	0.8037	pathogenic	-1.17	Destabilizing	0.996	D	0.813	deleterious	None	None	None	None	I
L/P	0.6024	likely_pathogenic	0.5233	ambiguous	-1.356	Destabilizing	0.995	D	0.813	deleterious	N	0.468130008	None	None	I
L/Q	0.6398	likely_pathogenic	0.5745	pathogenic	-1.33	Destabilizing	0.995	D	0.793	deleterious	N	0.468890477	None	None	I
L/R	0.7117	likely_pathogenic	0.6689	pathogenic	-0.738	Destabilizing	0.995	D	0.794	deleterious	N	0.475891916	None	None	I
L/S	0.8186	likely_pathogenic	0.7473	pathogenic	-1.842	Destabilizing	0.988	D	0.792	deleterious	None	None	None	None	I
L/T	0.5491	ambiguous	0.487	ambiguous	-1.682	Destabilizing	0.919	D	0.754	deleterious	None	None	None	None	I
L/V	0.0826	likely_benign	0.0794	benign	-1.356	Destabilizing	0.046	N	0.232	neutral	N	0.384780811	None	None	I
L/W	0.8371	likely_pathogenic	0.7962	pathogenic	-1.583	Destabilizing	0.999	D	0.772	deleterious	None	None	None	None	I
L/Y	0.8339	likely_pathogenic	0.792	pathogenic	-1.372	Destabilizing	0.996	D	0.748	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.