TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14638	44137;44138;44139	chr2:178631136;178631135;178631134	chr2:179495863;179495862;179495861
N2AB	12997	39214;39215;39216	chr2:178631136;178631135;178631134	chr2:179495863;179495862;179495861
N2A	12070	36433;36434;36435	chr2:178631136;178631135;178631134	chr2:179495863;179495862;179495861
N2B	5573	16942;16943;16944	chr2:178631136;178631135;178631134	chr2:179495863;179495862;179495861
Novex-1	5698	17317;17318;17319	chr2:178631136;178631135;178631134	chr2:179495863;179495862;179495861
Novex-2	5765	17518;17519;17520	chr2:178631136;178631135;178631134	chr2:179495863;179495862;179495861
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: Ig-97
• Domain position: 53
• Structural Position: 134
• Q(SASA): 0.5863
• 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	rs878896650	None	0.014	N	0.265	0.106	0.181679512989	gnomAD-4.0.0	4.10636E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39758E-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	0.6662	likely_pathogenic	0.5985	pathogenic	-0.517	Destabilizing	0.86	D	0.663	neutral	None	None	None	None	N
K/C	0.8856	likely_pathogenic	0.8525	pathogenic	-0.653	Destabilizing	0.998	D	0.725	prob.delet.	None	None	None	None	N
K/D	0.7668	likely_pathogenic	0.7162	pathogenic	-0.161	Destabilizing	0.978	D	0.718	prob.delet.	None	None	None	None	N
K/E	0.2935	likely_benign	0.2532	benign	-0.094	Destabilizing	0.822	D	0.623	neutral	D	0.537723489	None	None	N
K/F	0.8886	likely_pathogenic	0.8684	pathogenic	-0.442	Destabilizing	0.998	D	0.718	prob.delet.	None	None	None	None	N
K/G	0.6219	likely_pathogenic	0.5668	pathogenic	-0.829	Destabilizing	0.956	D	0.669	neutral	None	None	None	None	N
K/H	0.5563	ambiguous	0.5147	ambiguous	-1.185	Destabilizing	0.994	D	0.683	prob.neutral	None	None	None	None	N
K/I	0.6259	likely_pathogenic	0.5607	ambiguous	0.264	Stabilizing	0.978	D	0.738	prob.delet.	None	None	None	None	N
K/L	0.5761	likely_pathogenic	0.5013	ambiguous	0.264	Stabilizing	0.956	D	0.669	neutral	None	None	None	None	N
K/M	0.3874	ambiguous	0.3359	benign	0.255	Stabilizing	0.997	D	0.678	prob.neutral	D	0.632341433	None	None	N
K/N	0.5215	ambiguous	0.4472	ambiguous	-0.356	Destabilizing	0.942	D	0.667	neutral	N	0.509549711	None	None	N
K/P	0.8529	likely_pathogenic	0.7772	pathogenic	0.034	Stabilizing	0.993	D	0.711	prob.delet.	None	None	None	None	N
K/Q	0.2168	likely_benign	0.1883	benign	-0.569	Destabilizing	0.942	D	0.673	neutral	N	0.500752876	None	None	N
K/R	0.0967	likely_benign	0.0873	benign	-0.47	Destabilizing	0.014	N	0.265	neutral	N	0.511272088	None	None	N
K/S	0.6473	likely_pathogenic	0.5762	pathogenic	-1.033	Destabilizing	0.86	D	0.657	neutral	None	None	None	None	N
K/T	0.3963	ambiguous	0.3336	benign	-0.78	Destabilizing	0.942	D	0.683	prob.neutral	N	0.491499853	None	None	N
K/V	0.6209	likely_pathogenic	0.541	ambiguous	0.034	Stabilizing	0.978	D	0.731	prob.delet.	None	None	None	None	N
K/W	0.8749	likely_pathogenic	0.8635	pathogenic	-0.285	Destabilizing	0.998	D	0.713	prob.delet.	None	None	None	None	N
K/Y	0.7798	likely_pathogenic	0.7573	pathogenic	0.034	Stabilizing	0.993	D	0.715	prob.delet.	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.