TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32115	96568;96569;96570	chr2:178543630;178543629;178543628	chr2:179408357;179408356;179408355
N2AB	30474	91645;91646;91647	chr2:178543630;178543629;178543628	chr2:179408357;179408356;179408355
N2A	29547	88864;88865;88866	chr2:178543630;178543629;178543628	chr2:179408357;179408356;179408355
N2B	23050	69373;69374;69375	chr2:178543630;178543629;178543628	chr2:179408357;179408356;179408355
Novex-1	23175	69748;69749;69750	chr2:178543630;178543629;178543628	chr2:179408357;179408356;179408355
Novex-2	23242	69949;69950;69951	chr2:178543630;178543629;178543628	chr2:179408357;179408356;179408355
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-122
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.5958
• 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
K/M	None	None	0.999	N	0.673	0.506	0.391775403332	gnomAD-4.0.0	1.62657E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87821E-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
K/A	0.5373	ambiguous	0.5588	ambiguous	-0.084	Destabilizing	0.999	D	0.668	neutral	None	None	None	None	N
K/C	0.7673	likely_pathogenic	0.7702	pathogenic	-0.287	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
K/D	0.843	likely_pathogenic	0.8376	pathogenic	0.139	Stabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
K/E	0.4048	ambiguous	0.3884	ambiguous	0.171	Stabilizing	0.995	D	0.612	neutral	N	0.467359335	None	None	N
K/F	0.9049	likely_pathogenic	0.9116	pathogenic	-0.156	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
K/G	0.6667	likely_pathogenic	0.6676	pathogenic	-0.326	Destabilizing	1.0	D	0.62	neutral	None	None	None	None	N
K/H	0.4228	ambiguous	0.4446	ambiguous	-0.571	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
K/I	0.5634	ambiguous	0.599	pathogenic	0.485	Stabilizing	0.989	D	0.729	prob.delet.	None	None	None	None	N
K/L	0.5343	ambiguous	0.5586	ambiguous	0.485	Stabilizing	0.989	D	0.62	neutral	None	None	None	None	N
K/M	0.3645	ambiguous	0.3696	ambiguous	0.225	Stabilizing	0.999	D	0.673	neutral	N	0.467787613	None	None	N
K/N	0.7229	likely_pathogenic	0.7158	pathogenic	0.103	Stabilizing	1.0	D	0.693	prob.neutral	N	0.467280634	None	None	N
K/P	0.9528	likely_pathogenic	0.9492	pathogenic	0.325	Stabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
K/Q	0.195	likely_benign	0.2031	benign	-0.039	Destabilizing	0.997	D	0.668	neutral	N	0.494604651	None	None	N
K/R	0.0855	likely_benign	0.0872	benign	-0.122	Destabilizing	0.992	D	0.565	neutral	N	0.493911218	None	None	N
K/S	0.629	likely_pathogenic	0.6174	pathogenic	-0.437	Destabilizing	0.999	D	0.648	neutral	None	None	None	None	N
K/T	0.2611	likely_benign	0.2579	benign	-0.239	Destabilizing	0.999	D	0.702	prob.neutral	N	0.408599033	None	None	N
K/V	0.4806	ambiguous	0.5164	ambiguous	0.325	Stabilizing	0.992	D	0.692	prob.neutral	None	None	None	None	N
K/W	0.8309	likely_pathogenic	0.8286	pathogenic	-0.135	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
K/Y	0.8078	likely_pathogenic	0.8158	pathogenic	0.201	Stabilizing	0.998	D	0.689	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.