TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15935	48028;48029;48030	chr2:178617192;178617191;178617190	chr2:179481919;179481918;179481917
N2AB	14294	43105;43106;43107	chr2:178617192;178617191;178617190	chr2:179481919;179481918;179481917
N2A	13367	40324;40325;40326	chr2:178617192;178617191;178617190	chr2:179481919;179481918;179481917
N2B	6870	20833;20834;20835	chr2:178617192;178617191;178617190	chr2:179481919;179481918;179481917
Novex-1	6995	21208;21209;21210	chr2:178617192;178617191;178617190	chr2:179481919;179481918;179481917
Novex-2	7062	21409;21410;21411	chr2:178617192;178617191;178617190	chr2:179481919;179481918;179481917
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-3
• Domain position: 77
• Structural Position: 109
• Q(SASA): 0.0895
• 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	None	None	0.811	N	0.569	0.1	0.16115917748	gnomAD-4.0.0	6.99974E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.22127E-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
S/A	0.1181	likely_benign	0.1155	benign	-1.472	Destabilizing	0.48	N	0.462	neutral	N	0.462716778	None	None	N
S/C	0.0757	likely_benign	0.0633	benign	-1.266	Destabilizing	0.036	N	0.623	neutral	N	0.471592597	None	None	N
S/D	0.8461	likely_pathogenic	0.8363	pathogenic	-2.206	Highly Destabilizing	0.932	D	0.662	neutral	None	None	None	None	N
S/E	0.7798	likely_pathogenic	0.7551	pathogenic	-2.002	Highly Destabilizing	0.872	D	0.662	neutral	None	None	None	None	N
S/F	0.2133	likely_benign	0.2017	benign	-1.124	Destabilizing	0.007	N	0.505	neutral	N	0.466178421	None	None	N
S/G	0.2218	likely_benign	0.2115	benign	-1.805	Destabilizing	0.85	D	0.581	neutral	None	None	None	None	N
S/H	0.4368	ambiguous	0.3897	ambiguous	-1.873	Destabilizing	0.993	D	0.715	prob.delet.	None	None	None	None	N
S/I	0.2004	likely_benign	0.2104	benign	-0.615	Destabilizing	0.083	N	0.645	neutral	None	None	None	None	N
S/K	0.7316	likely_pathogenic	0.6806	pathogenic	-0.796	Destabilizing	0.773	D	0.636	neutral	None	None	None	None	N
S/L	0.1321	likely_benign	0.1324	benign	-0.615	Destabilizing	0.584	D	0.698	prob.neutral	None	None	None	None	N
S/M	0.1896	likely_benign	0.1946	benign	-0.908	Destabilizing	0.98	D	0.711	prob.delet.	None	None	None	None	N
S/N	0.3664	ambiguous	0.3602	ambiguous	-1.42	Destabilizing	0.932	D	0.669	neutral	None	None	None	None	N
S/P	0.9871	likely_pathogenic	0.985	pathogenic	-0.873	Destabilizing	0.991	D	0.733	prob.delet.	D	0.6100278	None	None	N
S/Q	0.5909	likely_pathogenic	0.5471	ambiguous	-1.175	Destabilizing	0.96	D	0.71	prob.delet.	None	None	None	None	N
S/R	0.5643	likely_pathogenic	0.4928	ambiguous	-1.047	Destabilizing	0.021	N	0.615	neutral	None	None	None	None	N
S/T	0.123	likely_benign	0.1251	benign	-1.096	Destabilizing	0.811	D	0.569	neutral	N	0.472369536	None	None	N
S/V	0.2289	likely_benign	0.2405	benign	-0.873	Destabilizing	0.584	D	0.687	prob.neutral	None	None	None	None	N
S/W	0.3877	ambiguous	0.3456	ambiguous	-1.394	Destabilizing	0.998	D	0.739	prob.delet.	None	None	None	None	N
S/Y	0.211	likely_benign	0.1856	benign	-1.016	Destabilizing	0.719	D	0.713	prob.delet.	N	0.465115061	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.