TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18893	56902;56903;56904	chr2:178599033;178599032;178599031	chr2:179463760;179463759;179463758
N2AB	17252	51979;51980;51981	chr2:178599033;178599032;178599031	chr2:179463760;179463759;179463758
N2A	16325	49198;49199;49200	chr2:178599033;178599032;178599031	chr2:179463760;179463759;179463758
N2B	9828	29707;29708;29709	chr2:178599033;178599032;178599031	chr2:179463760;179463759;179463758
Novex-1	9953	30082;30083;30084	chr2:178599033;178599032;178599031	chr2:179463760;179463759;179463758
Novex-2	10020	30283;30284;30285	chr2:178599033;178599032;178599031	chr2:179463760;179463759;179463758
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-25
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.4163
• 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
V/A	rs758414408	-0.913	0.958	N	0.599	0.326	0.571207575158	gnomAD-2.1.1	4.44E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.61E-06	0
V/A	rs758414408	-0.913	0.958	N	0.599	0.326	0.571207575158	gnomAD-4.0.0	1.67082E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.98381E-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
V/A	0.7491	likely_pathogenic	0.7582	pathogenic	-1.433	Destabilizing	0.958	D	0.599	neutral	N	0.515884001	None	None	N
V/C	0.9339	likely_pathogenic	0.932	pathogenic	-1.191	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
V/D	0.9915	likely_pathogenic	0.9919	pathogenic	-0.987	Destabilizing	0.998	D	0.832	deleterious	N	0.501939571	None	None	N
V/E	0.9726	likely_pathogenic	0.9734	pathogenic	-0.996	Destabilizing	0.998	D	0.82	deleterious	None	None	None	None	N
V/F	0.6825	likely_pathogenic	0.7151	pathogenic	-1.301	Destabilizing	0.988	D	0.829	deleterious	N	0.479019015	None	None	N
V/G	0.9176	likely_pathogenic	0.9124	pathogenic	-1.742	Destabilizing	0.994	D	0.811	deleterious	N	0.510142324	None	None	N
V/H	0.9896	likely_pathogenic	0.9913	pathogenic	-1.35	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
V/I	0.0669	likely_benign	0.0728	benign	-0.691	Destabilizing	0.067	N	0.305	neutral	N	0.465361967	None	None	N
V/K	0.978	likely_pathogenic	0.9803	pathogenic	-1.029	Destabilizing	0.995	D	0.823	deleterious	None	None	None	None	N
V/L	0.3595	ambiguous	0.4277	ambiguous	-0.691	Destabilizing	0.618	D	0.486	neutral	N	0.511056971	None	None	N
V/M	0.4704	ambiguous	0.5406	ambiguous	-0.573	Destabilizing	0.991	D	0.768	deleterious	None	None	None	None	N
V/N	0.9635	likely_pathogenic	0.9672	pathogenic	-0.815	Destabilizing	0.998	D	0.84	deleterious	None	None	None	None	N
V/P	0.9404	likely_pathogenic	0.9362	pathogenic	-0.903	Destabilizing	0.998	D	0.837	deleterious	None	None	None	None	N
V/Q	0.9692	likely_pathogenic	0.9725	pathogenic	-0.982	Destabilizing	0.998	D	0.843	deleterious	None	None	None	None	N
V/R	0.9646	likely_pathogenic	0.9669	pathogenic	-0.598	Destabilizing	0.998	D	0.838	deleterious	None	None	None	None	N
V/S	0.9212	likely_pathogenic	0.9217	pathogenic	-1.406	Destabilizing	0.995	D	0.815	deleterious	None	None	None	None	N
V/T	0.7652	likely_pathogenic	0.8027	pathogenic	-1.289	Destabilizing	0.968	D	0.715	prob.delet.	None	None	None	None	N
V/W	0.9911	likely_pathogenic	0.9931	pathogenic	-1.437	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
V/Y	0.9606	likely_pathogenic	0.9652	pathogenic	-1.125	Destabilizing	0.995	D	0.839	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.