TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28468	85627;85628;85629	chr2:178560730;178560729;178560728	chr2:179425457;179425456;179425455
N2AB	26827	80704;80705;80706	chr2:178560730;178560729;178560728	chr2:179425457;179425456;179425455
N2A	25900	77923;77924;77925	chr2:178560730;178560729;178560728	chr2:179425457;179425456;179425455
N2B	19403	58432;58433;58434	chr2:178560730;178560729;178560728	chr2:179425457;179425456;179425455
Novex-1	19528	58807;58808;58809	chr2:178560730;178560729;178560728	chr2:179425457;179425456;179425455
Novex-2	19595	59008;59009;59010	chr2:178560730;178560729;178560728	chr2:179425457;179425456;179425455
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Fn3-95
• Domain position: 19
• Structural Position: 20
• Q(SASA): 0.0888
• 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
C/G	None	None	0.684	N	0.775	0.441	0.696495078693	gnomAD-4.0.0	1.3685E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.31884E-05	0
C/R	rs1553563147	None	0.939	N	0.841	0.482	0.716165656389	gnomAD-4.0.0	2.737E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59782E-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
C/A	0.5687	likely_pathogenic	0.5687	pathogenic	-1.529	Destabilizing	0.037	N	0.316	neutral	None	None	None	None	N
C/D	0.9959	likely_pathogenic	0.9966	pathogenic	-0.973	Destabilizing	0.953	D	0.835	deleterious	None	None	None	None	N
C/E	0.9972	likely_pathogenic	0.9977	pathogenic	-0.753	Destabilizing	0.953	D	0.829	deleterious	None	None	None	None	N
C/F	0.543	ambiguous	0.6118	pathogenic	-1.126	Destabilizing	0.884	D	0.822	deleterious	N	0.481974167	None	None	N
C/G	0.4557	ambiguous	0.4779	ambiguous	-1.888	Destabilizing	0.684	D	0.775	deleterious	N	0.508347309	None	None	N
C/H	0.9869	likely_pathogenic	0.9903	pathogenic	-2.223	Highly Destabilizing	0.996	D	0.815	deleterious	None	None	None	None	N
C/I	0.5555	ambiguous	0.5355	ambiguous	-0.576	Destabilizing	0.59	D	0.796	deleterious	None	None	None	None	N
C/K	0.997	likely_pathogenic	0.9976	pathogenic	-0.64	Destabilizing	0.91	D	0.803	deleterious	None	None	None	None	N
C/L	0.5679	likely_pathogenic	0.5816	pathogenic	-0.576	Destabilizing	0.17	N	0.677	prob.neutral	None	None	None	None	N
C/M	0.7561	likely_pathogenic	0.765	pathogenic	-0.008	Destabilizing	0.206	N	0.579	neutral	None	None	None	None	N
C/N	0.9802	likely_pathogenic	0.9844	pathogenic	-1.195	Destabilizing	0.953	D	0.841	deleterious	None	None	None	None	N
C/P	0.9964	likely_pathogenic	0.9971	pathogenic	-0.869	Destabilizing	0.953	D	0.841	deleterious	None	None	None	None	N
C/Q	0.9888	likely_pathogenic	0.9914	pathogenic	-0.781	Destabilizing	0.953	D	0.843	deleterious	None	None	None	None	N
C/R	0.9776	likely_pathogenic	0.9828	pathogenic	-1.112	Destabilizing	0.939	D	0.841	deleterious	N	0.520717572	None	None	N
C/S	0.7699	likely_pathogenic	0.7909	pathogenic	-1.533	Destabilizing	0.521	D	0.771	deleterious	N	0.502106338	None	None	N
C/T	0.8325	likely_pathogenic	0.8315	pathogenic	-1.104	Destabilizing	0.742	D	0.787	deleterious	None	None	None	None	N
C/V	0.4503	ambiguous	0.4256	ambiguous	-0.869	Destabilizing	0.59	D	0.734	prob.delet.	None	None	None	None	N
C/W	0.9607	likely_pathogenic	0.9666	pathogenic	-1.415	Destabilizing	0.994	D	0.791	deleterious	N	0.520717572	None	None	N
C/Y	0.8406	likely_pathogenic	0.8717	pathogenic	-1.19	Destabilizing	0.939	D	0.805	deleterious	N	0.520210593	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.