TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17089	51490;51491;51492	chr2:178610261;178610260;178610259	chr2:179474988;179474987;179474986
N2AB	15448	46567;46568;46569	chr2:178610261;178610260;178610259	chr2:179474988;179474987;179474986
N2A	14521	43786;43787;43788	chr2:178610261;178610260;178610259	chr2:179474988;179474987;179474986
N2B	8024	24295;24296;24297	chr2:178610261;178610260;178610259	chr2:179474988;179474987;179474986
Novex-1	8149	24670;24671;24672	chr2:178610261;178610260;178610259	chr2:179474988;179474987;179474986
Novex-2	8216	24871;24872;24873	chr2:178610261;178610260;178610259	chr2:179474988;179474987;179474986
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-12
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.238
• 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
A/G	None	None	1.0	N	0.588	0.371	0.370051654043	gnomAD-4.0.0	1.59282E-06	None	None	None	None	N	None	0	0	None	0	2.7767E-05	None	0	0	0	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
A/C	0.8394	likely_pathogenic	0.832	pathogenic	-0.726	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
A/D	0.9369	likely_pathogenic	0.9116	pathogenic	-0.496	Destabilizing	1.0	D	0.731	prob.delet.	N	0.506224368	None	None	N
A/E	0.879	likely_pathogenic	0.8413	pathogenic	-0.563	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
A/F	0.8371	likely_pathogenic	0.8168	pathogenic	-0.729	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
A/G	0.4017	ambiguous	0.3757	ambiguous	-0.748	Destabilizing	1.0	D	0.588	neutral	N	0.490564269	None	None	N
A/H	0.9245	likely_pathogenic	0.9034	pathogenic	-0.73	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
A/I	0.6845	likely_pathogenic	0.6559	pathogenic	-0.193	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
A/K	0.9457	likely_pathogenic	0.9279	pathogenic	-0.896	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
A/L	0.569	likely_pathogenic	0.5626	ambiguous	-0.193	Destabilizing	1.0	D	0.662	neutral	None	None	None	None	N
A/M	0.5722	likely_pathogenic	0.5507	ambiguous	-0.303	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	N
A/N	0.7611	likely_pathogenic	0.7376	pathogenic	-0.569	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
A/P	0.8172	likely_pathogenic	0.8104	pathogenic	-0.272	Destabilizing	1.0	D	0.715	prob.delet.	N	0.485273092	None	None	N
A/Q	0.819	likely_pathogenic	0.7915	pathogenic	-0.739	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
A/R	0.9173	likely_pathogenic	0.8916	pathogenic	-0.508	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
A/S	0.1968	likely_benign	0.1852	benign	-0.911	Destabilizing	1.0	D	0.605	neutral	N	0.466455258	None	None	N
A/T	0.3341	likely_benign	0.2961	benign	-0.878	Destabilizing	1.0	D	0.685	prob.neutral	N	0.48280879	None	None	N
A/V	0.4253	ambiguous	0.3829	ambiguous	-0.272	Destabilizing	1.0	D	0.655	neutral	N	0.4528326	None	None	N
A/W	0.9734	likely_pathogenic	0.9684	pathogenic	-0.988	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
A/Y	0.905	likely_pathogenic	0.8851	pathogenic	-0.6	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.