TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17901	53926;53927;53928	chr2:178605594;178605593;178605592	chr2:179470321;179470320;179470319
N2AB	16260	49003;49004;49005	chr2:178605594;178605593;178605592	chr2:179470321;179470320;179470319
N2A	15333	46222;46223;46224	chr2:178605594;178605593;178605592	chr2:179470321;179470320;179470319
N2B	8836	26731;26732;26733	chr2:178605594;178605593;178605592	chr2:179470321;179470320;179470319
Novex-1	8961	27106;27107;27108	chr2:178605594;178605593;178605592	chr2:179470321;179470320;179470319
Novex-2	9028	27307;27308;27309	chr2:178605594;178605593;178605592	chr2:179470321;179470320;179470319
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-18
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.1525
• 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/N	None	None	0.085	N	0.449	0.17	0.177238962908	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
K/T	None	None	0.978	N	0.771	0.446	0.352910780287	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
K/A	0.7754	likely_pathogenic	0.8168	pathogenic	-1.388	Destabilizing	0.944	D	0.707	prob.neutral	None	None	None	None	N
K/C	0.6685	likely_pathogenic	0.7394	pathogenic	-1.475	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
K/D	0.9872	likely_pathogenic	0.9913	pathogenic	-2.212	Highly Destabilizing	0.968	D	0.756	deleterious	None	None	None	None	N
K/E	0.7678	likely_pathogenic	0.8133	pathogenic	-1.885	Destabilizing	0.928	D	0.689	prob.neutral	N	0.48882793	None	None	N
K/F	0.8942	likely_pathogenic	0.9163	pathogenic	-0.605	Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
K/G	0.8713	likely_pathogenic	0.9136	pathogenic	-1.889	Destabilizing	0.895	D	0.739	prob.delet.	None	None	None	None	N
K/H	0.6169	likely_pathogenic	0.6521	pathogenic	-1.612	Destabilizing	0.996	D	0.802	deleterious	None	None	None	None	N
K/I	0.6811	likely_pathogenic	0.7478	pathogenic	0.052	Stabilizing	0.989	D	0.85	deleterious	N	0.497988886	None	None	N
K/L	0.6371	likely_pathogenic	0.7087	pathogenic	0.052	Stabilizing	0.992	D	0.775	deleterious	None	None	None	None	N
K/M	0.3149	likely_benign	0.3631	ambiguous	-0.33	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
K/N	0.9311	likely_pathogenic	0.9477	pathogenic	-2.023	Highly Destabilizing	0.085	N	0.449	neutral	N	0.506932185	None	None	N
K/P	0.9977	likely_pathogenic	0.9983	pathogenic	-0.409	Destabilizing	0.992	D	0.819	deleterious	None	None	None	None	N
K/Q	0.2876	likely_benign	0.3205	benign	-1.605	Destabilizing	0.978	D	0.801	deleterious	N	0.467431992	None	None	N
K/R	0.1165	likely_benign	0.1187	benign	-0.929	Destabilizing	0.928	D	0.705	prob.neutral	N	0.474709382	None	None	N
K/S	0.8566	likely_pathogenic	0.8816	pathogenic	-2.503	Highly Destabilizing	0.895	D	0.683	prob.neutral	None	None	None	None	N
K/T	0.5994	likely_pathogenic	0.6985	pathogenic	-1.907	Destabilizing	0.978	D	0.771	deleterious	N	0.513054339	None	None	N
K/V	0.5768	likely_pathogenic	0.6566	pathogenic	-0.409	Destabilizing	0.992	D	0.805	deleterious	None	None	None	None	N
K/W	0.8932	likely_pathogenic	0.9147	pathogenic	-0.699	Destabilizing	0.999	D	0.796	deleterious	None	None	None	None	N
K/Y	0.7351	likely_pathogenic	0.7589	pathogenic	-0.343	Destabilizing	0.997	D	0.843	deleterious	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.