TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6811	20656;20657;20658	chr2:178725891;178725890;178725889	chr2:179590618;179590617;179590616
N2AB	6494	19705;19706;19707	chr2:178725891;178725890;178725889	chr2:179590618;179590617;179590616
N2A	5567	16924;16925;16926	chr2:178725891;178725890;178725889	chr2:179590618;179590617;179590616
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: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-52
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.6124
• 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/P	None	None	0.754	D	0.659	0.22	0.152612264143	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
S/A	0.0813	likely_benign	0.0714	benign	-0.286	Destabilizing	None	N	0.255	neutral	D	0.532960757	None	None	N
S/C	0.185	likely_benign	0.1674	benign	-0.228	Destabilizing	0.007	N	0.46	neutral	D	0.530499348	None	None	N
S/D	0.6628	likely_pathogenic	0.6115	pathogenic	0.232	Stabilizing	0.222	N	0.581	neutral	None	None	None	None	N
S/E	0.6855	likely_pathogenic	0.6471	pathogenic	0.136	Stabilizing	0.444	N	0.582	neutral	None	None	None	None	N
S/F	0.2785	likely_benign	0.2221	benign	-0.894	Destabilizing	0.012	N	0.493	neutral	N	0.497391483	None	None	N
S/G	0.1515	likely_benign	0.1226	benign	-0.392	Destabilizing	0.179	N	0.523	neutral	None	None	None	None	N
S/H	0.501	ambiguous	0.4429	ambiguous	-0.937	Destabilizing	0.938	D	0.628	neutral	None	None	None	None	N
S/I	0.2597	likely_benign	0.2099	benign	-0.142	Destabilizing	0.789	D	0.684	prob.neutral	None	None	None	None	N
S/K	0.813	likely_pathogenic	0.7787	pathogenic	-0.385	Destabilizing	0.681	D	0.583	neutral	None	None	None	None	N
S/L	0.1342	likely_benign	0.115	benign	-0.142	Destabilizing	0.517	D	0.633	neutral	None	None	None	None	N
S/M	0.2898	likely_benign	0.2379	benign	0.076	Stabilizing	0.938	D	0.629	neutral	None	None	None	None	N
S/N	0.2686	likely_benign	0.2076	benign	-0.107	Destabilizing	0.001	N	0.323	neutral	None	None	None	None	N
S/P	0.546	ambiguous	0.4922	ambiguous	-0.161	Destabilizing	0.754	D	0.659	neutral	D	0.529037804	None	None	N
S/Q	0.6043	likely_pathogenic	0.5578	ambiguous	-0.358	Destabilizing	0.938	D	0.628	neutral	None	None	None	None	N
S/R	0.7526	likely_pathogenic	0.723	pathogenic	-0.219	Destabilizing	0.882	D	0.651	neutral	None	None	None	None	N
S/T	0.1006	likely_benign	0.0931	benign	-0.213	Destabilizing	None	N	0.321	neutral	N	0.489731708	None	None	N
S/V	0.2086	likely_benign	0.1709	benign	-0.161	Destabilizing	0.286	N	0.635	neutral	None	None	None	None	N
S/W	0.4804	ambiguous	0.4278	ambiguous	-0.91	Destabilizing	0.994	D	0.66	neutral	None	None	None	None	N
S/Y	0.2591	likely_benign	0.2185	benign	-0.617	Destabilizing	0.739	D	0.693	prob.neutral	N	0.488401808	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.