TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28692	86299;86300;86301	chr2:178560058;178560057;178560056	chr2:179424785;179424784;179424783
N2AB	27051	81376;81377;81378	chr2:178560058;178560057;178560056	chr2:179424785;179424784;179424783
N2A	26124	78595;78596;78597	chr2:178560058;178560057;178560056	chr2:179424785;179424784;179424783
N2B	19627	59104;59105;59106	chr2:178560058;178560057;178560056	chr2:179424785;179424784;179424783
Novex-1	19752	59479;59480;59481	chr2:178560058;178560057;178560056	chr2:179424785;179424784;179424783
Novex-2	19819	59680;59681;59682	chr2:178560058;178560057;178560056	chr2:179424785;179424784;179424783
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: Fn3-97
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.5269
• 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	None	None	None	N	0.08	0.111	0.0401082797425	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
K/R	None	None	None	N	0.105	0.116	0.0611884634855	gnomAD-4.0.0	1.59151E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85817E-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	0.2478	likely_benign	0.1995	benign	-0.811	Destabilizing	None	N	0.138	neutral	None	None	None	None	N
K/C	0.5185	ambiguous	0.4448	ambiguous	-0.77	Destabilizing	0.676	D	0.298	neutral	None	None	None	None	N
K/D	0.5346	ambiguous	0.4588	ambiguous	-0.351	Destabilizing	0.038	N	0.271	neutral	None	None	None	None	N
K/E	0.1629	likely_benign	0.1427	benign	-0.219	Destabilizing	0.012	N	0.191	neutral	N	0.460123932	None	None	N
K/F	0.6594	likely_pathogenic	0.5878	pathogenic	-0.431	Destabilizing	0.214	N	0.346	neutral	None	None	None	None	N
K/G	0.3594	ambiguous	0.3044	benign	-1.2	Destabilizing	0.016	N	0.27	neutral	None	None	None	None	N
K/H	0.3029	likely_benign	0.2645	benign	-1.495	Destabilizing	0.356	N	0.323	neutral	None	None	None	None	N
K/I	0.2436	likely_benign	0.1948	benign	0.211	Stabilizing	None	N	0.241	neutral	N	0.516212075	None	None	N
K/L	0.1825	likely_benign	0.1498	benign	0.211	Stabilizing	0.006	N	0.277	neutral	None	None	None	None	N
K/M	0.138	likely_benign	0.113	benign	0.123	Stabilizing	0.002	N	0.226	neutral	None	None	None	None	N
K/N	0.3039	likely_benign	0.2483	benign	-0.717	Destabilizing	None	N	0.08	neutral	N	0.494796652	None	None	N
K/P	0.4059	ambiguous	0.3558	ambiguous	-0.1	Destabilizing	0.136	N	0.359	neutral	None	None	None	None	N
K/Q	0.1092	likely_benign	0.0975	benign	-0.761	Destabilizing	0.001	N	0.086	neutral	N	0.503818781	None	None	N
K/R	0.0819	likely_benign	0.0789	benign	-0.725	Destabilizing	None	N	0.105	neutral	N	0.486697244	None	None	N
K/S	0.3368	likely_benign	0.2625	benign	-1.396	Destabilizing	0.016	N	0.171	neutral	None	None	None	None	N
K/T	0.1688	likely_benign	0.1161	benign	-1.046	Destabilizing	None	N	0.19	neutral	N	0.475864175	None	None	N
K/V	0.2176	likely_benign	0.1712	benign	-0.1	Destabilizing	0.006	N	0.274	neutral	None	None	None	None	N
K/W	0.7196	likely_pathogenic	0.6666	pathogenic	-0.287	Destabilizing	0.864	D	0.319	neutral	None	None	None	None	N
K/Y	0.5471	ambiguous	0.4782	ambiguous	-0.009	Destabilizing	0.356	N	0.33	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.