TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28738	86437;86438;86439	chr2:178559920;178559919;178559918	chr2:179424647;179424646;179424645
N2AB	27097	81514;81515;81516	chr2:178559920;178559919;178559918	chr2:179424647;179424646;179424645
N2A	26170	78733;78734;78735	chr2:178559920;178559919;178559918	chr2:179424647;179424646;179424645
N2B	19673	59242;59243;59244	chr2:178559920;178559919;178559918	chr2:179424647;179424646;179424645
Novex-1	19798	59617;59618;59619	chr2:178559920;178559919;178559918	chr2:179424647;179424646;179424645
Novex-2	19865	59818;59819;59820	chr2:178559920;178559919;178559918	chr2:179424647;179424646;179424645
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-97
• Domain position: 88
• Structural Position: 122
• Q(SASA): 0.4843
• 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
D/G	None	None	0.181	N	0.541	0.148	0.186928172975	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
D/A	0.1324	likely_benign	0.1271	benign	-0.402	Destabilizing	0.044	N	0.528	neutral	N	0.426934078	None	None	N
D/C	0.4748	ambiguous	0.4599	ambiguous	0.065	Stabilizing	0.96	D	0.659	prob.neutral	None	None	None	None	N
D/E	0.1008	likely_benign	0.0978	benign	-0.288	Destabilizing	None	N	0.189	neutral	N	0.392914718	None	None	N
D/F	0.3948	ambiguous	0.3973	ambiguous	-0.372	Destabilizing	0.864	D	0.619	neutral	None	None	None	None	N
D/G	0.1841	likely_benign	0.184	benign	-0.575	Destabilizing	0.181	N	0.541	neutral	N	0.472090364	None	None	N
D/H	0.2769	likely_benign	0.2616	benign	-0.2	Destabilizing	0.612	D	0.542	neutral	N	0.488041252	None	None	N
D/I	0.1921	likely_benign	0.1783	benign	0.002	Stabilizing	0.676	D	0.658	prob.neutral	None	None	None	None	N
D/K	0.3378	likely_benign	0.311	benign	0.396	Stabilizing	0.057	N	0.519	neutral	None	None	None	None	N
D/L	0.2261	likely_benign	0.2088	benign	0.002	Stabilizing	0.227	N	0.645	neutral	None	None	None	None	N
D/M	0.4095	ambiguous	0.4014	ambiguous	0.218	Stabilizing	0.96	D	0.627	neutral	None	None	None	None	N
D/N	0.1061	likely_benign	0.1055	benign	0.068	Stabilizing	0.181	N	0.388	neutral	N	0.466087112	None	None	N
D/P	0.3984	ambiguous	0.3916	ambiguous	-0.113	Destabilizing	None	N	0.3	neutral	None	None	None	None	N
D/Q	0.2758	likely_benign	0.2571	benign	0.084	Stabilizing	0.128	N	0.411	neutral	None	None	None	None	N
D/R	0.4022	ambiguous	0.3807	ambiguous	0.5	Stabilizing	0.507	D	0.651	prob.neutral	None	None	None	None	N
D/S	0.1129	likely_benign	0.1135	benign	-0.021	Destabilizing	0.057	N	0.445	neutral	None	None	None	None	N
D/T	0.1781	likely_benign	0.1731	benign	0.12	Stabilizing	0.227	N	0.563	neutral	None	None	None	None	N
D/V	0.1295	likely_benign	0.1174	benign	-0.113	Destabilizing	0.181	N	0.635	neutral	N	0.475650744	None	None	N
D/W	0.8225	likely_pathogenic	0.817	pathogenic	-0.22	Destabilizing	0.96	D	0.67	prob.neutral	None	None	None	None	N
D/Y	0.1912	likely_benign	0.1841	benign	-0.129	Destabilizing	0.828	D	0.619	neutral	N	0.499431681	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.