TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21484	64675;64676;64677	chr2:178585294;178585293;178585292	chr2:179450021;179450020;179450019
N2AB	19843	59752;59753;59754	chr2:178585294;178585293;178585292	chr2:179450021;179450020;179450019
N2A	18916	56971;56972;56973	chr2:178585294;178585293;178585292	chr2:179450021;179450020;179450019
N2B	12419	37480;37481;37482	chr2:178585294;178585293;178585292	chr2:179450021;179450020;179450019
Novex-1	12544	37855;37856;37857	chr2:178585294;178585293;178585292	chr2:179450021;179450020;179450019
Novex-2	12611	38056;38057;38058	chr2:178585294;178585293;178585292	chr2:179450021;179450020;179450019
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-124
• Domain position: 16
• Structural Position: 28
• Q(SASA): 0.184
• 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
L/P	None	None	1.0	N	0.869	0.533	0.735635039567	gnomAD-4.0.0	1.59651E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86628E-06	0	0
L/V	None	None	0.992	N	0.556	0.278	0.341226946553	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
L/A	0.7739	likely_pathogenic	0.6807	pathogenic	-2.161	Highly Destabilizing	0.997	D	0.691	prob.neutral	None	None	None	None	N
L/C	0.7789	likely_pathogenic	0.7292	pathogenic	-1.517	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
L/D	0.9976	likely_pathogenic	0.9944	pathogenic	-2.167	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
L/E	0.9845	likely_pathogenic	0.9683	pathogenic	-1.95	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
L/F	0.5463	ambiguous	0.4292	ambiguous	-1.213	Destabilizing	0.999	D	0.785	deleterious	N	0.512507261	None	None	N
L/G	0.9548	likely_pathogenic	0.9196	pathogenic	-2.68	Highly Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
L/H	0.9619	likely_pathogenic	0.9174	pathogenic	-1.931	Destabilizing	1.0	D	0.859	deleterious	N	0.484764735	None	None	N
L/I	0.1824	likely_benign	0.1589	benign	-0.682	Destabilizing	0.992	D	0.55	neutral	N	0.489494328	None	None	N
L/K	0.9737	likely_pathogenic	0.9444	pathogenic	-1.768	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
L/M	0.1988	likely_benign	0.1759	benign	-0.634	Destabilizing	0.967	D	0.344	neutral	None	None	None	None	N
L/N	0.9845	likely_pathogenic	0.9665	pathogenic	-2.139	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
L/P	0.9929	likely_pathogenic	0.9859	pathogenic	-1.153	Destabilizing	1.0	D	0.869	deleterious	N	0.484764735	None	None	N
L/Q	0.926	likely_pathogenic	0.8526	pathogenic	-1.984	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/R	0.9574	likely_pathogenic	0.9133	pathogenic	-1.495	Destabilizing	0.999	D	0.843	deleterious	N	0.502615501	None	None	N
L/S	0.9686	likely_pathogenic	0.9331	pathogenic	-2.836	Highly Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
L/T	0.8706	likely_pathogenic	0.7966	pathogenic	-2.461	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
L/V	0.1998	likely_benign	0.1749	benign	-1.153	Destabilizing	0.992	D	0.556	neutral	N	0.447604846	None	None	N
L/W	0.9112	likely_pathogenic	0.8412	pathogenic	-1.51	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
L/Y	0.8969	likely_pathogenic	0.8227	pathogenic	-1.202	Destabilizing	1.0	D	0.852	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.