TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19406	58441;58442;58443	chr2:178594177;178594176;178594175	chr2:179458904;179458903;179458902
N2AB	17765	53518;53519;53520	chr2:178594177;178594176;178594175	chr2:179458904;179458903;179458902
N2A	16838	50737;50738;50739	chr2:178594177;178594176;178594175	chr2:179458904;179458903;179458902
N2B	10341	31246;31247;31248	chr2:178594177;178594176;178594175	chr2:179458904;179458903;179458902
Novex-1	10466	31621;31622;31623	chr2:178594177;178594176;178594175	chr2:179458904;179458903;179458902
Novex-2	10533	31822;31823;31824	chr2:178594177;178594176;178594175	chr2:179458904;179458903;179458902
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-118
• Domain position: 16
• Structural Position: 30
• Q(SASA): 0.1897
• 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
L/F	None	None	0.982	N	0.699	0.314	0.627153701111	gnomAD-4.0.0	1.59225E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43312E-05	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
L/A	0.9262	likely_pathogenic	0.9178	pathogenic	-2.048	Highly Destabilizing	0.953	D	0.714	prob.delet.	None	None	None	None	N
L/C	0.9127	likely_pathogenic	0.9115	pathogenic	-1.3	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
L/D	0.9989	likely_pathogenic	0.9987	pathogenic	-2.501	Highly Destabilizing	0.998	D	0.826	deleterious	None	None	None	None	N
L/E	0.9934	likely_pathogenic	0.9924	pathogenic	-2.226	Highly Destabilizing	0.993	D	0.847	deleterious	None	None	None	None	N
L/F	0.4299	ambiguous	0.3975	ambiguous	-1.293	Destabilizing	0.982	D	0.699	prob.neutral	N	0.487378304	None	None	N
L/G	0.9894	likely_pathogenic	0.9869	pathogenic	-2.571	Highly Destabilizing	0.993	D	0.848	deleterious	None	None	None	None	N
L/H	0.9842	likely_pathogenic	0.9832	pathogenic	-2.144	Highly Destabilizing	0.999	D	0.813	deleterious	D	0.613362505	None	None	N
L/I	0.125	likely_benign	0.1216	benign	-0.506	Destabilizing	0.17	N	0.375	neutral	D	0.532742832	None	None	N
L/K	0.9882	likely_pathogenic	0.9868	pathogenic	-1.462	Destabilizing	0.993	D	0.827	deleterious	None	None	None	None	N
L/M	0.2382	likely_benign	0.2298	benign	-0.585	Destabilizing	0.807	D	0.575	neutral	None	None	None	None	N
L/N	0.9945	likely_pathogenic	0.9942	pathogenic	-2.019	Highly Destabilizing	0.998	D	0.837	deleterious	None	None	None	None	N
L/P	0.9882	likely_pathogenic	0.9853	pathogenic	-1.007	Destabilizing	0.997	D	0.828	deleterious	D	0.613362505	None	None	N
L/Q	0.9753	likely_pathogenic	0.9716	pathogenic	-1.734	Destabilizing	0.993	D	0.817	deleterious	None	None	None	None	N
L/R	0.981	likely_pathogenic	0.9759	pathogenic	-1.577	Destabilizing	0.991	D	0.817	deleterious	D	0.613362505	None	None	N
L/S	0.9904	likely_pathogenic	0.9889	pathogenic	-2.602	Highly Destabilizing	0.993	D	0.828	deleterious	None	None	None	None	N
L/T	0.9655	likely_pathogenic	0.9649	pathogenic	-2.165	Highly Destabilizing	0.986	D	0.771	deleterious	None	None	None	None	N
L/V	0.1783	likely_benign	0.1739	benign	-1.007	Destabilizing	0.17	N	0.364	neutral	D	0.556633968	None	None	N
L/W	0.9208	likely_pathogenic	0.91	pathogenic	-1.598	Destabilizing	0.999	D	0.788	deleterious	None	None	None	None	N
L/Y	0.9473	likely_pathogenic	0.9414	pathogenic	-1.286	Destabilizing	0.993	D	0.724	prob.delet.	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.