TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23944	72055;72056;72057	chr2:178574302;178574301;178574300	chr2:179439029;179439028;179439027
N2AB	22303	67132;67133;67134	chr2:178574302;178574301;178574300	chr2:179439029;179439028;179439027
N2A	21376	64351;64352;64353	chr2:178574302;178574301;178574300	chr2:179439029;179439028;179439027
N2B	14879	44860;44861;44862	chr2:178574302;178574301;178574300	chr2:179439029;179439028;179439027
Novex-1	15004	45235;45236;45237	chr2:178574302;178574301;178574300	chr2:179439029;179439028;179439027
Novex-2	15071	45436;45437;45438	chr2:178574302;178574301;178574300	chr2:179439029;179439028;179439027
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-62
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.2103
• 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/N	rs1449315408	None	0.005	N	0.186	0.078	0.132336055621	gnomAD-4.0.0	3.42169E-06	None	None	None	None	N	None	0	0	None	0	2.52564E-05	None	0	0	0	0	6.62734E-05

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	0.3233	likely_benign	0.3005	benign	-0.878	Destabilizing	0.103	N	0.401	neutral	None	None	None	None	N
K/C	0.5431	ambiguous	0.4963	ambiguous	-0.803	Destabilizing	0.991	D	0.581	neutral	None	None	None	None	N
K/D	0.7583	likely_pathogenic	0.7324	pathogenic	-0.549	Destabilizing	0.209	N	0.407	neutral	None	None	None	None	N
K/E	0.2136	likely_benign	0.2082	benign	-0.358	Destabilizing	0.166	N	0.339	neutral	N	0.442423605	None	None	N
K/F	0.7333	likely_pathogenic	0.7122	pathogenic	-0.183	Destabilizing	0.901	D	0.569	neutral	None	None	None	None	N
K/G	0.4825	ambiguous	0.4566	ambiguous	-1.32	Destabilizing	0.209	N	0.49	neutral	None	None	None	None	N
K/H	0.259	likely_benign	0.2424	benign	-1.504	Destabilizing	0.901	D	0.541	neutral	None	None	None	None	N
K/I	0.3202	likely_benign	0.3264	benign	0.319	Stabilizing	0.873	D	0.614	neutral	N	0.478616479	None	None	N
K/L	0.3295	likely_benign	0.3352	benign	0.319	Stabilizing	0.561	D	0.519	neutral	None	None	None	None	N
K/M	0.2	likely_benign	0.1973	benign	0.076	Stabilizing	0.901	D	0.54	neutral	None	None	None	None	N
K/N	0.473	ambiguous	0.4565	ambiguous	-0.961	Destabilizing	0.005	N	0.186	neutral	N	0.499682397	None	None	N
K/P	0.9584	likely_pathogenic	0.9644	pathogenic	-0.052	Destabilizing	0.722	D	0.494	neutral	None	None	None	None	N
K/Q	0.0911	likely_benign	0.0893	benign	-0.845	Destabilizing	0.005	N	0.204	neutral	N	0.4055988	None	None	N
K/R	0.0773	likely_benign	0.0781	benign	-0.857	Destabilizing	0.166	N	0.333	neutral	N	0.447714782	None	None	N
K/S	0.3496	ambiguous	0.3186	benign	-1.589	Destabilizing	0.007	N	0.211	neutral	None	None	None	None	N
K/T	0.1596	likely_benign	0.1515	benign	-1.169	Destabilizing	0.166	N	0.408	neutral	N	0.44881086	None	None	N
K/V	0.3083	likely_benign	0.3097	benign	-0.052	Destabilizing	0.561	D	0.531	neutral	None	None	None	None	N
K/W	0.7422	likely_pathogenic	0.7238	pathogenic	-0.114	Destabilizing	0.991	D	0.611	neutral	None	None	None	None	N
K/Y	0.5969	likely_pathogenic	0.5668	pathogenic	0.162	Stabilizing	0.965	D	0.599	neutral	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.