TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24655	74188;74189;74190	chr2:178572169;178572168;178572167	chr2:179436896;179436895;179436894
N2AB	23014	69265;69266;69267	chr2:178572169;178572168;178572167	chr2:179436896;179436895;179436894
N2A	22087	66484;66485;66486	chr2:178572169;178572168;178572167	chr2:179436896;179436895;179436894
N2B	15590	46993;46994;46995	chr2:178572169;178572168;178572167	chr2:179436896;179436895;179436894
Novex-1	15715	47368;47369;47370	chr2:178572169;178572168;178572167	chr2:179436896;179436895;179436894
Novex-2	15782	47569;47570;47571	chr2:178572169;178572168;178572167	chr2:179436896;179436895;179436894
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-67
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.1137
• 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
M/T	rs1575757808	None	0.9	N	0.553	0.406	0.605101485313	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
M/A	0.896	likely_pathogenic	0.892	pathogenic	-2.168	Highly Destabilizing	0.942	D	0.553	neutral	None	None	None	None	N
M/C	0.8833	likely_pathogenic	0.8766	pathogenic	-1.732	Destabilizing	1.0	D	0.607	neutral	None	None	None	None	N
M/D	0.9979	likely_pathogenic	0.9978	pathogenic	-1.353	Destabilizing	0.988	D	0.665	neutral	None	None	None	None	N
M/E	0.9706	likely_pathogenic	0.9715	pathogenic	-1.109	Destabilizing	0.828	D	0.573	neutral	None	None	None	None	N
M/F	0.5341	ambiguous	0.5181	ambiguous	-0.696	Destabilizing	0.976	D	0.608	neutral	None	None	None	None	N
M/G	0.9557	likely_pathogenic	0.9561	pathogenic	-2.679	Highly Destabilizing	0.975	D	0.597	neutral	None	None	None	None	N
M/H	0.9231	likely_pathogenic	0.9166	pathogenic	-2.181	Highly Destabilizing	0.992	D	0.653	neutral	None	None	None	None	N
M/I	0.8482	likely_pathogenic	0.7997	pathogenic	-0.697	Destabilizing	0.918	D	0.659	neutral	N	0.476285463	None	None	N
M/K	0.6199	likely_pathogenic	0.5804	pathogenic	-0.974	Destabilizing	0.735	D	0.59	neutral	N	0.457603701	None	None	N
M/L	0.4195	ambiguous	0.3689	ambiguous	-0.697	Destabilizing	0.499	N	0.508	neutral	N	0.501469122	None	None	N
M/N	0.9625	likely_pathogenic	0.9639	pathogenic	-1.337	Destabilizing	0.977	D	0.643	neutral	None	None	None	None	N
M/P	0.9995	likely_pathogenic	0.9994	pathogenic	-1.168	Destabilizing	0.996	D	0.642	neutral	None	None	None	None	N
M/Q	0.7186	likely_pathogenic	0.72	pathogenic	-0.991	Destabilizing	0.943	D	0.613	neutral	None	None	None	None	N
M/R	0.7022	likely_pathogenic	0.6659	pathogenic	-1.157	Destabilizing	0.036	N	0.417	neutral	N	0.47374659	None	None	N
M/S	0.9199	likely_pathogenic	0.9233	pathogenic	-2.005	Highly Destabilizing	0.975	D	0.578	neutral	None	None	None	None	N
M/T	0.8844	likely_pathogenic	0.8737	pathogenic	-1.615	Destabilizing	0.9	D	0.553	neutral	N	0.5091286	None	None	N
M/V	0.4474	ambiguous	0.376	ambiguous	-1.168	Destabilizing	0.912	D	0.637	neutral	N	0.506317581	None	None	N
M/W	0.9258	likely_pathogenic	0.9009	pathogenic	-0.937	Destabilizing	1.0	D	0.619	neutral	None	None	None	None	N
M/Y	0.7594	likely_pathogenic	0.7434	pathogenic	-0.925	Destabilizing	0.998	D	0.614	neutral	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.