TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16878	50857;50858;50859	chr2:178611597;178611596;178611595	chr2:179476324;179476323;179476322
N2AB	15237	45934;45935;45936	chr2:178611597;178611596;178611595	chr2:179476324;179476323;179476322
N2A	14310	43153;43154;43155	chr2:178611597;178611596;178611595	chr2:179476324;179476323;179476322
N2B	7813	23662;23663;23664	chr2:178611597;178611596;178611595	chr2:179476324;179476323;179476322
Novex-1	7938	24037;24038;24039	chr2:178611597;178611596;178611595	chr2:179476324;179476323;179476322
Novex-2	8005	24238;24239;24240	chr2:178611597;178611596;178611595	chr2:179476324;179476323;179476322
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-11
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.4573
• 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
K/E	None	None	0.989	N	0.436	0.269	0.345632371893	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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
K/A	0.5894	likely_pathogenic	0.6123	pathogenic	-0.005	Destabilizing	0.996	D	0.482	neutral	None	None	None	None	I
K/C	0.8299	likely_pathogenic	0.8326	pathogenic	-0.124	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
K/D	0.7683	likely_pathogenic	0.7691	pathogenic	0.011	Stabilizing	0.999	D	0.617	neutral	None	None	None	None	I
K/E	0.3036	likely_benign	0.3258	benign	0.006	Stabilizing	0.989	D	0.436	neutral	N	0.457475616	None	None	I
K/F	0.8657	likely_pathogenic	0.8676	pathogenic	-0.265	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	I
K/G	0.7163	likely_pathogenic	0.7073	pathogenic	-0.197	Destabilizing	0.999	D	0.517	neutral	None	None	None	None	I
K/H	0.4353	ambiguous	0.4121	ambiguous	-0.553	Destabilizing	1.0	D	0.595	neutral	None	None	None	None	I
K/I	0.5095	ambiguous	0.5496	ambiguous	0.421	Stabilizing	0.999	D	0.697	prob.neutral	N	0.473570693	None	None	I
K/L	0.5734	likely_pathogenic	0.5658	pathogenic	0.421	Stabilizing	0.999	D	0.517	neutral	None	None	None	None	I
K/M	0.3714	ambiguous	0.3708	ambiguous	0.332	Stabilizing	1.0	D	0.587	neutral	None	None	None	None	I
K/N	0.5333	ambiguous	0.5442	ambiguous	0.288	Stabilizing	0.998	D	0.559	neutral	N	0.429104035	None	None	I
K/P	0.9807	likely_pathogenic	0.9795	pathogenic	0.307	Stabilizing	1.0	D	0.612	neutral	None	None	None	None	I
K/Q	0.1882	likely_benign	0.1871	benign	0.062	Stabilizing	0.997	D	0.568	neutral	N	0.470027381	None	None	I
K/R	0.1039	likely_benign	0.0975	benign	-0.018	Destabilizing	0.217	N	0.174	neutral	N	0.445430326	None	None	I
K/S	0.6092	likely_pathogenic	0.6293	pathogenic	-0.199	Destabilizing	0.996	D	0.49	neutral	None	None	None	None	I
K/T	0.3081	likely_benign	0.3355	benign	-0.062	Destabilizing	0.998	D	0.543	neutral	N	0.459942895	None	None	I
K/V	0.4685	ambiguous	0.4994	ambiguous	0.307	Stabilizing	0.999	D	0.639	neutral	None	None	None	None	I
K/W	0.8886	likely_pathogenic	0.8718	pathogenic	-0.263	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
K/Y	0.7481	likely_pathogenic	0.7272	pathogenic	0.098	Stabilizing	1.0	D	0.64	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.