TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26350	79273;79274;79275	chr2:178567084;178567083;178567082	chr2:179431811;179431810;179431809
N2AB	24709	74350;74351;74352	chr2:178567084;178567083;178567082	chr2:179431811;179431810;179431809
N2A	23782	71569;71570;71571	chr2:178567084;178567083;178567082	chr2:179431811;179431810;179431809
N2B	17285	52078;52079;52080	chr2:178567084;178567083;178567082	chr2:179431811;179431810;179431809
Novex-1	17410	52453;52454;52455	chr2:178567084;178567083;178567082	chr2:179431811;179431810;179431809
Novex-2	17477	52654;52655;52656	chr2:178567084;178567083;178567082	chr2:179431811;179431810;179431809
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: Fn3-79
• Domain position: 65
• Structural Position: 96
• Q(SASA): 0.794
• 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/R	rs1278375861	0.239	0.142	N	0.271	0.182	0.297375071883	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
K/R	rs1278375861	0.239	0.142	N	0.271	0.182	0.297375071883	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
K/R	rs1278375861	0.239	0.142	N	0.271	0.182	0.297375071883	gnomAD-4.0.0	3.09891E-06	None	None	None	None	N	None	0	0	None	0	4.45911E-05	None	0	0	2.54318E-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	0.8539	likely_pathogenic	0.8442	pathogenic	0.028	Stabilizing	0.968	D	0.608	neutral	None	None	None	None	N
K/C	0.9034	likely_pathogenic	0.893	pathogenic	-0.42	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
K/D	0.9223	likely_pathogenic	0.9043	pathogenic	-0.172	Destabilizing	0.995	D	0.702	prob.neutral	None	None	None	None	N
K/E	0.866	likely_pathogenic	0.8386	pathogenic	-0.169	Destabilizing	0.958	D	0.581	neutral	N	0.51945745	None	None	N
K/F	0.9835	likely_pathogenic	0.9813	pathogenic	-0.242	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
K/G	0.7399	likely_pathogenic	0.7065	pathogenic	-0.128	Destabilizing	0.991	D	0.644	neutral	None	None	None	None	N
K/H	0.5279	ambiguous	0.4807	ambiguous	-0.202	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
K/I	0.9636	likely_pathogenic	0.9621	pathogenic	0.359	Stabilizing	0.994	D	0.721	prob.delet.	N	0.495723556	None	None	N
K/L	0.8945	likely_pathogenic	0.8867	pathogenic	0.359	Stabilizing	0.991	D	0.644	neutral	None	None	None	None	N
K/M	0.8681	likely_pathogenic	0.8621	pathogenic	-0.059	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	N
K/N	0.8205	likely_pathogenic	0.7941	pathogenic	0.029	Stabilizing	0.988	D	0.733	prob.delet.	N	0.442436674	None	None	N
K/P	0.9654	likely_pathogenic	0.9645	pathogenic	0.274	Stabilizing	0.998	D	0.676	prob.neutral	None	None	None	None	N
K/Q	0.5124	ambiguous	0.4602	ambiguous	-0.096	Destabilizing	0.988	D	0.735	prob.delet.	N	0.494456108	None	None	N
K/R	0.0987	likely_benign	0.0851	benign	-0.038	Destabilizing	0.142	N	0.271	neutral	N	0.471319573	None	None	N
K/S	0.8449	likely_pathogenic	0.8267	pathogenic	-0.359	Destabilizing	0.968	D	0.655	neutral	None	None	None	None	N
K/T	0.8123	likely_pathogenic	0.8042	pathogenic	-0.228	Destabilizing	0.988	D	0.695	prob.neutral	N	0.47331366	None	None	N
K/V	0.9195	likely_pathogenic	0.9148	pathogenic	0.274	Stabilizing	0.995	D	0.679	prob.neutral	None	None	None	None	N
K/W	0.9658	likely_pathogenic	0.9549	pathogenic	-0.332	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
K/Y	0.9267	likely_pathogenic	0.9122	pathogenic	0.022	Stabilizing	0.998	D	0.699	prob.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.