TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19807	59644;59645;59646	chr2:178592586;178592585;178592584	chr2:179457313;179457312;179457311
N2AB	18166	54721;54722;54723	chr2:178592586;178592585;178592584	chr2:179457313;179457312;179457311
N2A	17239	51940;51941;51942	chr2:178592586;178592585;178592584	chr2:179457313;179457312;179457311
N2B	10742	32449;32450;32451	chr2:178592586;178592585;178592584	chr2:179457313;179457312;179457311
Novex-1	10867	32824;32825;32826	chr2:178592586;178592585;178592584	chr2:179457313;179457312;179457311
Novex-2	10934	33025;33026;33027	chr2:178592586;178592585;178592584	chr2:179457313;179457312;179457311
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-119
• Domain position: 18
• Structural Position: 31
• Q(SASA): 0.3799
• 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
S/R	None	None	0.994	N	0.593	0.479	0.517322629239	gnomAD-4.0.0	6.84331E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9958E-07	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
S/A	0.1444	likely_benign	0.1438	benign	-0.793	Destabilizing	0.931	D	0.447	neutral	None	None	None	None	N
S/C	0.2096	likely_benign	0.2074	benign	-0.424	Destabilizing	1.0	D	0.643	neutral	N	0.495318023	None	None	N
S/D	0.7878	likely_pathogenic	0.8084	pathogenic	-0.12	Destabilizing	0.995	D	0.485	neutral	None	None	None	None	N
S/E	0.7994	likely_pathogenic	0.8271	pathogenic	-0.099	Destabilizing	0.995	D	0.471	neutral	None	None	None	None	N
S/F	0.4319	ambiguous	0.4109	ambiguous	-0.932	Destabilizing	0.991	D	0.665	neutral	None	None	None	None	N
S/G	0.2157	likely_benign	0.2278	benign	-1.072	Destabilizing	0.98	D	0.469	neutral	N	0.501305504	None	None	N
S/H	0.5756	likely_pathogenic	0.5901	pathogenic	-1.506	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	N
S/I	0.4866	ambiguous	0.4939	ambiguous	-0.15	Destabilizing	0.925	D	0.59	neutral	D	0.528557801	None	None	N
S/K	0.9367	likely_pathogenic	0.9409	pathogenic	-0.622	Destabilizing	0.985	D	0.444	neutral	None	None	None	None	N
S/L	0.2447	likely_benign	0.2302	benign	-0.15	Destabilizing	0.871	D	0.497	neutral	None	None	None	None	N
S/M	0.3515	ambiguous	0.3418	ambiguous	0.11	Stabilizing	0.559	D	0.338	neutral	None	None	None	None	N
S/N	0.3696	ambiguous	0.3758	ambiguous	-0.616	Destabilizing	0.993	D	0.508	neutral	N	0.490652774	None	None	N
S/P	0.8575	likely_pathogenic	0.9024	pathogenic	-0.33	Destabilizing	0.999	D	0.598	neutral	None	None	None	None	N
S/Q	0.7211	likely_pathogenic	0.7484	pathogenic	-0.685	Destabilizing	0.996	D	0.515	neutral	None	None	None	None	N
S/R	0.8892	likely_pathogenic	0.9014	pathogenic	-0.599	Destabilizing	0.994	D	0.593	neutral	N	0.495559949	None	None	N
S/T	0.1553	likely_benign	0.1568	benign	-0.625	Destabilizing	0.98	D	0.495	neutral	N	0.46642912	None	None	N
S/V	0.4338	ambiguous	0.441	ambiguous	-0.33	Destabilizing	0.942	D	0.556	neutral	None	None	None	None	N
S/W	0.4765	ambiguous	0.5169	ambiguous	-0.924	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
S/Y	0.3549	ambiguous	0.352	ambiguous	-0.65	Destabilizing	0.999	D	0.684	prob.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.