TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30663	92212;92213;92214	chr2:178549735;178549734;178549733	chr2:179414462;179414461;179414460
N2AB	29022	87289;87290;87291	chr2:178549735;178549734;178549733	chr2:179414462;179414461;179414460
N2A	28095	84508;84509;84510	chr2:178549735;178549734;178549733	chr2:179414462;179414461;179414460
N2B	21598	65017;65018;65019	chr2:178549735;178549734;178549733	chr2:179414462;179414461;179414460
Novex-1	21723	65392;65393;65394	chr2:178549735;178549734;178549733	chr2:179414462;179414461;179414460
Novex-2	21790	65593;65594;65595	chr2:178549735;178549734;178549733	chr2:179414462;179414461;179414460
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-111
• Domain position: 45
• Structural Position: 54
• Q(SASA): 0.3803
• 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	rs1418513895	0.054	1.0	N	0.585	0.495	0.410734915765	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	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	0.3008	likely_benign	0.3243	benign	-0.153	Destabilizing	0.998	D	0.419	neutral	None	None	None	None	N
S/C	0.5639	ambiguous	0.6113	pathogenic	-0.376	Destabilizing	1.0	D	0.652	neutral	N	0.513630909	None	None	N
S/D	0.9417	likely_pathogenic	0.9404	pathogenic	0.051	Stabilizing	0.999	D	0.491	neutral	None	None	None	None	N
S/E	0.9593	likely_pathogenic	0.9555	pathogenic	-0.057	Destabilizing	0.999	D	0.483	neutral	None	None	None	None	N
S/F	0.8855	likely_pathogenic	0.9103	pathogenic	-0.847	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
S/G	0.328	likely_benign	0.3729	ambiguous	-0.213	Destabilizing	0.999	D	0.418	neutral	N	0.49258028	None	None	N
S/H	0.8808	likely_pathogenic	0.876	pathogenic	-0.565	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
S/I	0.8529	likely_pathogenic	0.8767	pathogenic	-0.13	Destabilizing	1.0	D	0.667	neutral	N	0.513377419	None	None	N
S/K	0.9826	likely_pathogenic	0.98	pathogenic	-0.426	Destabilizing	0.999	D	0.483	neutral	None	None	None	None	N
S/L	0.5001	ambiguous	0.5865	pathogenic	-0.13	Destabilizing	1.0	D	0.567	neutral	None	None	None	None	N
S/M	0.7181	likely_pathogenic	0.7761	pathogenic	-0.098	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
S/N	0.6646	likely_pathogenic	0.7151	pathogenic	-0.181	Destabilizing	0.999	D	0.471	neutral	N	0.50864581	None	None	N
S/P	0.9396	likely_pathogenic	0.9377	pathogenic	-0.112	Destabilizing	1.0	D	0.593	neutral	None	None	None	None	N
S/Q	0.9167	likely_pathogenic	0.9153	pathogenic	-0.414	Destabilizing	1.0	D	0.579	neutral	None	None	None	None	N
S/R	0.9704	likely_pathogenic	0.9703	pathogenic	-0.17	Destabilizing	1.0	D	0.585	neutral	N	0.477116003	None	None	N
S/T	0.245	likely_benign	0.3127	benign	-0.29	Destabilizing	0.999	D	0.408	neutral	N	0.508283238	None	None	N
S/V	0.7752	likely_pathogenic	0.8112	pathogenic	-0.112	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	N
S/W	0.9088	likely_pathogenic	0.9181	pathogenic	-0.92	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
S/Y	0.8434	likely_pathogenic	0.8698	pathogenic	-0.609	Destabilizing	1.0	D	0.705	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.