TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33699	101320;101321;101322	chr2:178535520;178535519;178535518	chr2:179400247;179400246;179400245
N2AB	32058	96397;96398;96399	chr2:178535520;178535519;178535518	chr2:179400247;179400246;179400245
N2A	31131	93616;93617;93618	chr2:178535520;178535519;178535518	chr2:179400247;179400246;179400245
N2B	24634	74125;74126;74127	chr2:178535520;178535519;178535518	chr2:179400247;179400246;179400245
Novex-1	24759	74500;74501;74502	chr2:178535520;178535519;178535518	chr2:179400247;179400246;179400245
Novex-2	24826	74701;74702;74703	chr2:178535520;178535519;178535518	chr2:179400247;179400246;179400245
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: Fn3-132
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.3366
• 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/T	rs1691031638	None	0.004	N	0.195	0.072	0.17258766438	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	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	0.099	likely_benign	0.109	benign	-0.495	Destabilizing	0.099	N	0.369	neutral	None	None	None	None	N
S/C	0.1498	likely_benign	0.1671	benign	-0.386	Destabilizing	0.998	D	0.613	neutral	N	0.491669221	None	None	N
S/D	0.5568	ambiguous	0.5761	pathogenic	-0.105	Destabilizing	0.878	D	0.497	neutral	None	None	None	None	N
S/E	0.6303	likely_pathogenic	0.6099	pathogenic	-0.172	Destabilizing	0.909	D	0.513	neutral	None	None	None	None	N
S/F	0.2535	likely_benign	0.2955	benign	-0.956	Destabilizing	0.995	D	0.693	prob.neutral	None	None	None	None	N
S/G	0.1422	likely_benign	0.1539	benign	-0.66	Destabilizing	0.91	D	0.457	neutral	N	0.475362165	None	None	N
S/H	0.5022	ambiguous	0.5071	ambiguous	-1.214	Destabilizing	1.0	D	0.61	neutral	None	None	None	None	N
S/I	0.2464	likely_benign	0.2474	benign	-0.185	Destabilizing	0.986	D	0.675	prob.neutral	N	0.492124494	None	None	N
S/K	0.8123	likely_pathogenic	0.7987	pathogenic	-0.664	Destabilizing	0.964	D	0.505	neutral	None	None	None	None	N
S/L	0.1243	likely_benign	0.1474	benign	-0.185	Destabilizing	0.931	D	0.568	neutral	None	None	None	None	N
S/M	0.2153	likely_benign	0.2444	benign	0.094	Stabilizing	1.0	D	0.608	neutral	None	None	None	None	N
S/N	0.1956	likely_benign	0.2101	benign	-0.479	Destabilizing	0.388	N	0.524	neutral	N	0.472551008	None	None	N
S/P	0.9248	likely_pathogenic	0.915	pathogenic	-0.257	Destabilizing	0.981	D	0.629	neutral	None	None	None	None	N
S/Q	0.6271	likely_pathogenic	0.6117	pathogenic	-0.708	Destabilizing	0.995	D	0.557	neutral	None	None	None	None	N
S/R	0.7335	likely_pathogenic	0.7108	pathogenic	-0.467	Destabilizing	0.993	D	0.639	neutral	N	0.472689139	None	None	N
S/T	0.0691	likely_benign	0.0739	benign	-0.528	Destabilizing	0.004	N	0.195	neutral	N	0.476037533	None	None	N
S/V	0.2269	likely_benign	0.2356	benign	-0.257	Destabilizing	0.834	D	0.549	neutral	None	None	None	None	N
S/W	0.4707	ambiguous	0.493	ambiguous	-0.949	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
S/Y	0.3063	likely_benign	0.323	benign	-0.682	Destabilizing	0.998	D	0.691	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.