TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22711	68356;68357;68358	chr2:178578899;178578898;178578897	chr2:179443626;179443625;179443624
N2AB	21070	63433;63434;63435	chr2:178578899;178578898;178578897	chr2:179443626;179443625;179443624
N2A	20143	60652;60653;60654	chr2:178578899;178578898;178578897	chr2:179443626;179443625;179443624
N2B	13646	41161;41162;41163	chr2:178578899;178578898;178578897	chr2:179443626;179443625;179443624
Novex-1	13771	41536;41537;41538	chr2:178578899;178578898;178578897	chr2:179443626;179443625;179443624
Novex-2	13838	41737;41738;41739	chr2:178578899;178578898;178578897	chr2:179443626;179443625;179443624
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-52
• Domain position: 69
• Structural Position: 100
• Q(SASA): 0.3004
• 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
G/A	None	None	1.0	N	0.728	0.459	0.494906320408	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
G/S	None	None	1.0	N	0.799	0.508	0.498194598333	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
G/A	0.4402	ambiguous	0.3962	ambiguous	-0.471	Destabilizing	1.0	D	0.728	prob.delet.	N	0.488888198	None	None	N
G/C	0.5406	ambiguous	0.5045	ambiguous	-0.843	Destabilizing	1.0	D	0.815	deleterious	D	0.540291355	None	None	N
G/D	0.3185	likely_benign	0.2572	benign	-1.042	Destabilizing	1.0	D	0.815	deleterious	N	0.478163776	None	None	N
G/E	0.5135	ambiguous	0.4502	ambiguous	-1.184	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
G/F	0.8341	likely_pathogenic	0.8074	pathogenic	-1.057	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
G/H	0.656	likely_pathogenic	0.6123	pathogenic	-0.843	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
G/I	0.8452	likely_pathogenic	0.8348	pathogenic	-0.454	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
G/K	0.7577	likely_pathogenic	0.7002	pathogenic	-1.208	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
G/L	0.8209	likely_pathogenic	0.7947	pathogenic	-0.454	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
G/M	0.7859	likely_pathogenic	0.7654	pathogenic	-0.41	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
G/N	0.2913	likely_benign	0.2623	benign	-0.769	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
G/P	0.9867	likely_pathogenic	0.9854	pathogenic	-0.423	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
G/Q	0.63	likely_pathogenic	0.5881	pathogenic	-1.065	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
G/R	0.6981	likely_pathogenic	0.641	pathogenic	-0.69	Destabilizing	1.0	D	0.854	deleterious	N	0.512525862	None	None	N
G/S	0.2344	likely_benign	0.2068	benign	-0.89	Destabilizing	1.0	D	0.799	deleterious	N	0.491659675	None	None	N
G/T	0.5081	ambiguous	0.4877	ambiguous	-0.971	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
G/V	0.7469	likely_pathogenic	0.723	pathogenic	-0.423	Destabilizing	1.0	D	0.843	deleterious	N	0.510323816	None	None	N
G/W	0.7287	likely_pathogenic	0.6926	pathogenic	-1.274	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
G/Y	0.6428	likely_pathogenic	0.6096	pathogenic	-0.93	Destabilizing	1.0	D	0.808	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.