TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21899	65920;65921;65922	chr2:178583108;178583107;178583106	chr2:179447835;179447834;179447833
N2AB	20258	60997;60998;60999	chr2:178583108;178583107;178583106	chr2:179447835;179447834;179447833
N2A	19331	58216;58217;58218	chr2:178583108;178583107;178583106	chr2:179447835;179447834;179447833
N2B	12834	38725;38726;38727	chr2:178583108;178583107;178583106	chr2:179447835;179447834;179447833
Novex-1	12959	39100;39101;39102	chr2:178583108;178583107;178583106	chr2:179447835;179447834;179447833
Novex-2	13026	39301;39302;39303	chr2:178583108;178583107;178583106	chr2:179447835;179447834;179447833
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: Ig-125
• Domain position: 34
• Structural Position: 50
• Q(SASA): 0.1324
• 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/R	None	None	0.64	N	0.355	0.144	0.178374595973	gnomAD-4.0.0	1.59618E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8661E-06	0	0
K/T	None	None	0.999	N	0.721	0.499	0.376921832658	gnomAD-4.0.0	1.59618E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8661E-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	0.9388	likely_pathogenic	0.9221	pathogenic	-0.962	Destabilizing	0.998	D	0.561	neutral	None	None	None	None	N
K/C	0.9228	likely_pathogenic	0.8986	pathogenic	-0.998	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
K/D	0.981	likely_pathogenic	0.9786	pathogenic	-0.323	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
K/E	0.8261	likely_pathogenic	0.7943	pathogenic	-0.209	Destabilizing	0.996	D	0.518	neutral	N	0.516118762	None	None	N
K/F	0.9578	likely_pathogenic	0.9466	pathogenic	-0.923	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
K/G	0.9563	likely_pathogenic	0.9473	pathogenic	-1.305	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
K/H	0.5987	likely_pathogenic	0.5709	pathogenic	-1.751	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
K/I	0.8751	likely_pathogenic	0.8354	pathogenic	-0.073	Destabilizing	1.0	D	0.831	deleterious	N	0.480782398	None	None	N
K/L	0.8309	likely_pathogenic	0.7769	pathogenic	-0.073	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
K/M	0.7019	likely_pathogenic	0.6446	pathogenic	None	Stabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
K/N	0.9308	likely_pathogenic	0.9205	pathogenic	-0.651	Destabilizing	0.999	D	0.708	prob.delet.	N	0.489531811	None	None	N
K/P	0.9938	likely_pathogenic	0.9927	pathogenic	-0.341	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
K/Q	0.4905	ambiguous	0.4428	ambiguous	-0.788	Destabilizing	0.999	D	0.697	prob.neutral	N	0.476022685	None	None	N
K/R	0.0983	likely_benign	0.0945	benign	-0.646	Destabilizing	0.64	D	0.355	neutral	N	0.450768156	None	None	N
K/S	0.9591	likely_pathogenic	0.952	pathogenic	-1.411	Destabilizing	0.998	D	0.574	neutral	None	None	None	None	N
K/T	0.9017	likely_pathogenic	0.8729	pathogenic	-1.084	Destabilizing	0.999	D	0.721	prob.delet.	N	0.489278321	None	None	N
K/V	0.8572	likely_pathogenic	0.8202	pathogenic	-0.341	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
K/W	0.9244	likely_pathogenic	0.9009	pathogenic	-0.749	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
K/Y	0.8443	likely_pathogenic	0.8206	pathogenic	-0.408	Destabilizing	1.0	D	0.816	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.