TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5599	17020;17021;17022	chr2:178732174;178732173;178732172	chr2:179596901;179596900;179596899
N2AB	5282	16069;16070;16071	chr2:178732174;178732173;178732172	chr2:179596901;179596900;179596899
N2A	4355	13288;13289;13290	chr2:178732174;178732173;178732172	chr2:179596901;179596900;179596899
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-39
• Domain position: 57
• Structural Position: 136
• Q(SASA): 0.0958
• 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
A/V	rs1194013551	None	0.996	N	0.628	0.31	0.343788945184	gnomAD-4.0.0	3.1825E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86566E-05	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	0.7407	likely_pathogenic	0.7508	pathogenic	-0.638	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
A/D	0.9716	likely_pathogenic	0.9815	pathogenic	-1.878	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
A/E	0.9578	likely_pathogenic	0.9675	pathogenic	-1.655	Destabilizing	0.999	D	0.779	deleterious	N	0.466910289	None	None	N
A/F	0.892	likely_pathogenic	0.9011	pathogenic	-0.366	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
A/G	0.2627	likely_benign	0.3192	benign	-1.14	Destabilizing	0.998	D	0.631	neutral	N	0.469831132	None	None	N
A/H	0.9678	likely_pathogenic	0.974	pathogenic	-1.83	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
A/I	0.7246	likely_pathogenic	0.6986	pathogenic	0.754	Stabilizing	0.999	D	0.819	deleterious	None	None	None	None	N
A/K	0.9846	likely_pathogenic	0.9887	pathogenic	-0.649	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
A/L	0.6703	likely_pathogenic	0.6693	pathogenic	0.754	Stabilizing	0.997	D	0.695	prob.neutral	None	None	None	None	N
A/M	0.7029	likely_pathogenic	0.7117	pathogenic	0.456	Stabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
A/N	0.9284	likely_pathogenic	0.9499	pathogenic	-0.992	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
A/P	0.885	likely_pathogenic	0.8821	pathogenic	0.339	Stabilizing	1.0	D	0.829	deleterious	N	0.455553983	None	None	N
A/Q	0.9456	likely_pathogenic	0.9537	pathogenic	-0.724	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
A/R	0.9628	likely_pathogenic	0.9704	pathogenic	-0.98	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
A/S	0.2517	likely_benign	0.2777	benign	-1.399	Destabilizing	0.992	D	0.622	neutral	N	0.488126104	None	None	N
A/T	0.3534	ambiguous	0.3611	ambiguous	-1.034	Destabilizing	0.884	D	0.48	neutral	N	0.45574134	None	None	N
A/V	0.38	ambiguous	0.3338	benign	0.339	Stabilizing	0.996	D	0.628	neutral	N	0.467097645	None	None	N
A/W	0.9871	likely_pathogenic	0.99	pathogenic	-1.249	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
A/Y	0.9496	likely_pathogenic	0.9574	pathogenic	-0.581	Destabilizing	1.0	D	0.833	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.