TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26552	79879;79880;79881	chr2:178566478;178566477;178566476	chr2:179431205;179431204;179431203
N2AB	24911	74956;74957;74958	chr2:178566478;178566477;178566476	chr2:179431205;179431204;179431203
N2A	23984	72175;72176;72177	chr2:178566478;178566477;178566476	chr2:179431205;179431204;179431203
N2B	17487	52684;52685;52686	chr2:178566478;178566477;178566476	chr2:179431205;179431204;179431203
Novex-1	17612	53059;53060;53061	chr2:178566478;178566477;178566476	chr2:179431205;179431204;179431203
Novex-2	17679	53260;53261;53262	chr2:178566478;178566477;178566476	chr2:179431205;179431204;179431203
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: Fn3-81
• Domain position: 66
• Structural Position: 96
• Q(SASA): 0.8844
• 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
K/N	rs1305128121	0.364	0.967	N	0.667	0.199	0.110078149338	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
K/N	rs1305128121	0.364	0.967	N	0.667	0.199	0.110078149338	gnomAD-4.0.0	7.95932E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.42938E-05	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	0.1932	likely_benign	0.1951	benign	-0.034	Destabilizing	0.845	D	0.523	neutral	None	None	None	None	N
K/C	0.4752	ambiguous	0.4851	ambiguous	-0.459	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
K/D	0.221	likely_benign	0.2177	benign	-0.17	Destabilizing	0.975	D	0.62	neutral	None	None	None	None	N
K/E	0.1235	likely_benign	0.1155	benign	-0.187	Destabilizing	0.944	D	0.572	neutral	N	0.446759484	None	None	N
K/F	0.642	likely_pathogenic	0.6413	pathogenic	-0.397	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	N
K/G	0.1748	likely_benign	0.1736	benign	-0.155	Destabilizing	0.033	N	0.363	neutral	None	None	None	None	N
K/H	0.1741	likely_benign	0.1767	benign	-0.269	Destabilizing	0.999	D	0.605	neutral	None	None	None	None	N
K/I	0.392	ambiguous	0.3857	ambiguous	0.198	Stabilizing	0.994	D	0.675	prob.neutral	N	0.464299715	None	None	N
K/L	0.2818	likely_benign	0.2795	benign	0.198	Stabilizing	0.987	D	0.575	neutral	None	None	None	None	N
K/M	0.2067	likely_benign	0.2011	benign	-0.078	Destabilizing	0.999	D	0.605	neutral	None	None	None	None	N
K/N	0.1531	likely_benign	0.1475	benign	0.008	Stabilizing	0.967	D	0.667	neutral	N	0.386881675	None	None	N
K/P	0.5178	ambiguous	0.5244	ambiguous	0.144	Stabilizing	0.996	D	0.624	neutral	None	None	None	None	N
K/Q	0.0977	likely_benign	0.0959	benign	-0.14	Destabilizing	0.994	D	0.672	neutral	N	0.451675962	None	None	N
K/R	0.0841	likely_benign	0.0842	benign	-0.099	Destabilizing	0.944	D	0.583	neutral	N	0.478351828	None	None	N
K/S	0.1791	likely_benign	0.1782	benign	-0.392	Destabilizing	0.916	D	0.587	neutral	None	None	None	None	N
K/T	0.1271	likely_benign	0.1285	benign	-0.29	Destabilizing	0.983	D	0.619	neutral	N	0.511733683	None	None	N
K/V	0.3034	likely_benign	0.3081	benign	0.144	Stabilizing	0.987	D	0.617	neutral	None	None	None	None	N
K/W	0.6747	likely_pathogenic	0.6861	pathogenic	-0.482	Destabilizing	0.999	D	0.704	prob.neutral	None	None	None	None	N
K/Y	0.4309	ambiguous	0.4384	ambiguous	-0.127	Destabilizing	0.996	D	0.641	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.