TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26101	78526;78527;78528	chr2:178567831;178567830;178567829	chr2:179432558;179432557;179432556
N2AB	24460	73603;73604;73605	chr2:178567831;178567830;178567829	chr2:179432558;179432557;179432556
N2A	23533	70822;70823;70824	chr2:178567831;178567830;178567829	chr2:179432558;179432557;179432556
N2B	17036	51331;51332;51333	chr2:178567831;178567830;178567829	chr2:179432558;179432557;179432556
Novex-1	17161	51706;51707;51708	chr2:178567831;178567830;178567829	chr2:179432558;179432557;179432556
Novex-2	17228	51907;51908;51909	chr2:178567831;178567830;178567829	chr2:179432558;179432557;179432556
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: Fn3-78
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.4208
• 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/T	rs749914062	-0.597	0.007	N	0.115	0.144	None	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.66E-05	0
K/T	rs749914062	-0.597	0.007	N	0.115	0.144	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/T	rs749914062	-0.597	0.007	N	0.115	0.144	None	gnomAD-4.0.0	1.53786E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.3941E-05	0	5.69087E-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	0.4236	ambiguous	0.4394	ambiguous	-0.587	Destabilizing	0.525	D	0.298	neutral	None	None	None	None	N
K/C	0.6627	likely_pathogenic	0.6624	pathogenic	-0.722	Destabilizing	0.998	D	0.332	neutral	None	None	None	None	N
K/D	0.6869	likely_pathogenic	0.715	pathogenic	-0.874	Destabilizing	0.842	D	0.272	neutral	None	None	None	None	N
K/E	0.3331	likely_benign	0.3924	ambiguous	-0.736	Destabilizing	0.625	D	0.247	neutral	N	0.416148576	None	None	N
K/F	0.8506	likely_pathogenic	0.8735	pathogenic	-0.129	Destabilizing	0.974	D	0.359	neutral	None	None	None	None	N
K/G	0.3709	ambiguous	0.3829	ambiguous	-0.996	Destabilizing	0.842	D	0.265	neutral	None	None	None	None	N
K/H	0.333	likely_benign	0.338	benign	-1.445	Destabilizing	0.991	D	0.319	neutral	None	None	None	None	N
K/I	0.6421	likely_pathogenic	0.6925	pathogenic	0.494	Stabilizing	0.801	D	0.361	neutral	N	0.464673242	None	None	N
K/L	0.4365	ambiguous	0.4718	ambiguous	0.494	Stabilizing	0.525	D	0.23	neutral	None	None	None	None	N
K/M	0.2813	likely_benign	0.3017	benign	0.387	Stabilizing	0.991	D	0.323	neutral	None	None	None	None	N
K/N	0.3915	ambiguous	0.4223	ambiguous	-0.982	Destabilizing	0.801	D	0.205	neutral	N	0.398946895	None	None	N
K/P	0.9437	likely_pathogenic	0.9499	pathogenic	0.164	Stabilizing	0.915	D	0.332	neutral	None	None	None	None	N
K/Q	0.1667	likely_benign	0.1879	benign	-0.976	Destabilizing	0.891	D	0.323	neutral	N	0.415591215	None	None	N
K/R	0.0872	likely_benign	0.0894	benign	-1.021	Destabilizing	0.891	D	0.219	neutral	N	0.396562737	None	None	N
K/S	0.3441	ambiguous	0.3488	ambiguous	-1.477	Destabilizing	0.525	D	0.285	neutral	None	None	None	None	N
K/T	0.1197	likely_benign	0.1201	benign	-1.132	Destabilizing	0.007	N	0.115	neutral	N	0.278193985	None	None	N
K/V	0.5468	ambiguous	0.5827	pathogenic	0.164	Stabilizing	0.525	D	0.261	neutral	None	None	None	None	N
K/W	0.8607	likely_pathogenic	0.8804	pathogenic	-0.117	Destabilizing	0.998	D	0.357	neutral	None	None	None	None	N
K/Y	0.7267	likely_pathogenic	0.757	pathogenic	0.203	Stabilizing	0.991	D	0.349	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.