TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1619	5080;5081;5082	chr2:178777009;178777008;178777007	chr2:179641736;179641735;179641734
N2AB	1619	5080;5081;5082	chr2:178777009;178777008;178777007	chr2:179641736;179641735;179641734
N2A	1619	5080;5081;5082	chr2:178777009;178777008;178777007	chr2:179641736;179641735;179641734
N2B	1573	4942;4943;4944	chr2:178777009;178777008;178777007	chr2:179641736;179641735;179641734
Novex-1	1573	4942;4943;4944	chr2:178777009;178777008;178777007	chr2:179641736;179641735;179641734
Novex-2	1573	4942;4943;4944	chr2:178777009;178777008;178777007	chr2:179641736;179641735;179641734
Novex-3	1619	5080;5081;5082	chr2:178777009;178777008;178777007	chr2:179641736;179641735;179641734

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-7
• Domain position: 64
• Structural Position: 143
• Q(SASA): 0.5287
• 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/A	None	None	0.91	N	0.443	0.115	0.107399877778	gnomAD-4.0.0	6.00161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56251E-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	0.0688	likely_benign	0.0669	benign	-0.555	Destabilizing	0.91	D	0.443	neutral	N	0.45492946	None	None	N
S/C	0.121	likely_benign	0.1104	benign	-0.39	Destabilizing	1.0	D	0.542	neutral	N	0.495447226	None	None	N
S/D	0.355	ambiguous	0.2811	benign	-0.144	Destabilizing	0.97	D	0.454	neutral	None	None	None	None	N
S/E	0.423	ambiguous	0.3583	ambiguous	-0.205	Destabilizing	0.942	D	0.449	neutral	None	None	None	None	N
S/F	0.1619	likely_benign	0.1481	benign	-1.021	Destabilizing	0.998	D	0.655	neutral	D	0.53508549	None	None	N
S/G	0.1094	likely_benign	0.097	benign	-0.722	Destabilizing	0.985	D	0.439	neutral	None	None	None	None	N
S/H	0.2689	likely_benign	0.2473	benign	-1.292	Destabilizing	0.999	D	0.512	neutral	None	None	None	None	N
S/I	0.1874	likely_benign	0.1635	benign	-0.234	Destabilizing	0.991	D	0.649	neutral	None	None	None	None	N
S/K	0.5228	ambiguous	0.4446	ambiguous	-0.572	Destabilizing	0.942	D	0.432	neutral	None	None	None	None	N
S/L	0.1024	likely_benign	0.0938	benign	-0.234	Destabilizing	0.97	D	0.531	neutral	None	None	None	None	N
S/M	0.1716	likely_benign	0.1642	benign	0.148	Stabilizing	1.0	D	0.513	neutral	None	None	None	None	N
S/N	0.1254	likely_benign	0.1065	benign	-0.403	Destabilizing	0.985	D	0.5	neutral	None	None	None	None	N
S/P	0.6565	likely_pathogenic	0.576	pathogenic	-0.31	Destabilizing	0.998	D	0.519	neutral	N	0.452729397	None	None	N
S/Q	0.3792	ambiguous	0.3512	ambiguous	-0.676	Destabilizing	0.746	D	0.255	neutral	None	None	None	None	N
S/R	0.441	ambiguous	0.3729	ambiguous	-0.378	Destabilizing	0.991	D	0.459	neutral	None	None	None	None	N
S/T	0.0756	likely_benign	0.0728	benign	-0.476	Destabilizing	0.248	N	0.239	neutral	N	0.447008665	None	None	N
S/V	0.1588	likely_benign	0.1464	benign	-0.31	Destabilizing	0.97	D	0.526	neutral	None	None	None	None	N
S/W	0.3672	ambiguous	0.3267	benign	-0.978	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
S/Y	0.1568	likely_benign	0.1395	benign	-0.709	Destabilizing	0.998	D	0.653	neutral	D	0.534897754	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.