TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22077	66454;66455;66456	chr2:178582140;178582139;178582138	chr2:179446867;179446866;179446865
N2AB	20436	61531;61532;61533	chr2:178582140;178582139;178582138	chr2:179446867;179446866;179446865
N2A	19509	58750;58751;58752	chr2:178582140;178582139;178582138	chr2:179446867;179446866;179446865
N2B	13012	39259;39260;39261	chr2:178582140;178582139;178582138	chr2:179446867;179446866;179446865
Novex-1	13137	39634;39635;39636	chr2:178582140;178582139;178582138	chr2:179446867;179446866;179446865
Novex-2	13204	39835;39836;39837	chr2:178582140;178582139;178582138	chr2:179446867;179446866;179446865
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: Fn3-48
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.5432
• Predicted PPI site: I

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	0.032	N	0.252	0.052	0.0986583533028	gnomAD-4.0.0	6.84686E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99651E-07	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	0.644	likely_pathogenic	0.5135	ambiguous	-0.231	Destabilizing	0.754	D	0.551	neutral	None	None	None	None	I
K/C	0.8413	likely_pathogenic	0.7965	pathogenic	-0.253	Destabilizing	0.998	D	0.735	prob.delet.	None	None	None	None	I
K/D	0.8045	likely_pathogenic	0.7205	pathogenic	-0.077	Destabilizing	0.754	D	0.593	neutral	None	None	None	None	I
K/E	0.483	ambiguous	0.3623	ambiguous	-0.015	Destabilizing	0.698	D	0.53	neutral	N	0.461990801	None	None	I
K/F	0.8837	likely_pathogenic	0.8435	pathogenic	-0.056	Destabilizing	0.993	D	0.68	prob.neutral	None	None	None	None	I
K/G	0.7142	likely_pathogenic	0.6057	pathogenic	-0.541	Destabilizing	0.754	D	0.56	neutral	None	None	None	None	I
K/H	0.4874	ambiguous	0.4248	ambiguous	-0.915	Destabilizing	0.978	D	0.631	neutral	None	None	None	None	I
K/I	0.5695	likely_pathogenic	0.4592	ambiguous	0.543	Stabilizing	0.978	D	0.689	prob.neutral	None	None	None	None	I
K/L	0.4958	ambiguous	0.4005	ambiguous	0.543	Stabilizing	0.956	D	0.579	neutral	None	None	None	None	I
K/M	0.3735	ambiguous	0.2787	benign	0.316	Stabilizing	0.992	D	0.611	neutral	N	0.476550253	None	None	I
K/N	0.567	likely_pathogenic	0.4718	ambiguous	-0.102	Destabilizing	0.032	N	0.252	neutral	N	0.491372345	None	None	I
K/P	0.9104	likely_pathogenic	0.8516	pathogenic	0.315	Stabilizing	0.978	D	0.636	neutral	None	None	None	None	I
K/Q	0.2396	likely_benign	0.1862	benign	-0.208	Destabilizing	0.126	N	0.241	neutral	N	0.512843696	None	None	I
K/R	0.1305	likely_benign	0.1207	benign	-0.461	Destabilizing	0.698	D	0.507	neutral	N	0.510574181	None	None	I
K/S	0.6729	likely_pathogenic	0.5503	ambiguous	-0.618	Destabilizing	0.754	D	0.513	neutral	None	None	None	None	I
K/T	0.3975	ambiguous	0.2771	benign	-0.377	Destabilizing	0.822	D	0.596	neutral	N	0.475266742	None	None	I
K/V	0.5504	ambiguous	0.4407	ambiguous	0.315	Stabilizing	0.956	D	0.611	neutral	None	None	None	None	I
K/W	0.8946	likely_pathogenic	0.8688	pathogenic	None	Stabilizing	0.998	D	0.729	prob.delet.	None	None	None	None	I
K/Y	0.7682	likely_pathogenic	0.71	pathogenic	0.287	Stabilizing	0.978	D	0.677	prob.neutral	None	None	None	None	I

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.