TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23495	70708;70709;70710	chr2:178575649;178575648;178575647	chr2:179440376;179440375;179440374
N2AB	21854	65785;65786;65787	chr2:178575649;178575648;178575647	chr2:179440376;179440375;179440374
N2A	20927	63004;63005;63006	chr2:178575649;178575648;178575647	chr2:179440376;179440375;179440374
N2B	14430	43513;43514;43515	chr2:178575649;178575648;178575647	chr2:179440376;179440375;179440374
Novex-1	14555	43888;43889;43890	chr2:178575649;178575648;178575647	chr2:179440376;179440375;179440374
Novex-2	14622	44089;44090;44091	chr2:178575649;178575648;178575647	chr2:179440376;179440375;179440374
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: Fn3-58
• Domain position: 61
• Structural Position: 92
• Q(SASA): 0.4908
• 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/E	None	None	0.87	N	0.541	0.215	0.245101548738	gnomAD-4.0.0	3.18337E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86607E-05	0
K/N	rs1482776876	-0.244	0.987	N	0.662	0.263	0.143124449307	gnomAD-2.1.1	2.01E-05	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	3.56E-05	0
K/N	rs1482776876	-0.244	0.987	N	0.662	0.263	0.143124449307	gnomAD-4.0.0	1.437E-05	None	None	None	None	N	None	2.98829E-05	0	None	0	0	None	0	0	1.52924E-05	0	4.97051E-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	0.556	ambiguous	0.6175	pathogenic	-0.588	Destabilizing	0.967	D	0.634	neutral	None	None	None	None	N
K/C	0.709	likely_pathogenic	0.756	pathogenic	-0.645	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
K/D	0.8377	likely_pathogenic	0.8589	pathogenic	0.074	Stabilizing	0.995	D	0.762	deleterious	None	None	None	None	N
K/E	0.3959	ambiguous	0.4275	ambiguous	0.171	Stabilizing	0.87	D	0.541	neutral	N	0.505704293	None	None	N
K/F	0.8678	likely_pathogenic	0.9027	pathogenic	-0.421	Destabilizing	0.999	D	0.734	prob.delet.	None	None	None	None	N
K/G	0.7443	likely_pathogenic	0.8002	pathogenic	-0.923	Destabilizing	0.99	D	0.701	prob.neutral	None	None	None	None	N
K/H	0.3279	likely_benign	0.3424	ambiguous	-1.245	Destabilizing	0.997	D	0.737	prob.delet.	None	None	None	None	N
K/I	0.428	ambiguous	0.4733	ambiguous	0.266	Stabilizing	0.823	D	0.753	deleterious	N	0.473659736	None	None	N
K/L	0.488	ambiguous	0.5219	ambiguous	0.266	Stabilizing	0.753	D	0.701	prob.neutral	None	None	None	None	N
K/M	0.3577	ambiguous	0.3833	ambiguous	0.157	Stabilizing	0.997	D	0.729	prob.delet.	None	None	None	None	N
K/N	0.7114	likely_pathogenic	0.7582	pathogenic	-0.376	Destabilizing	0.987	D	0.662	neutral	N	0.467734707	None	None	N
K/P	0.844	likely_pathogenic	0.8817	pathogenic	0.012	Stabilizing	0.998	D	0.762	deleterious	None	None	None	None	N
K/Q	0.1906	likely_benign	0.1999	benign	-0.468	Destabilizing	0.904	D	0.649	neutral	N	0.504069497	None	None	N
K/R	0.0701	likely_benign	0.0731	benign	-0.484	Destabilizing	0.013	N	0.245	neutral	N	0.443271754	None	None	N
K/S	0.6508	likely_pathogenic	0.6984	pathogenic	-1.079	Destabilizing	0.967	D	0.602	neutral	None	None	None	None	N
K/T	0.2454	likely_benign	0.2639	benign	-0.774	Destabilizing	0.959	D	0.751	deleterious	N	0.42981688	None	None	N
K/V	0.3836	ambiguous	0.4145	ambiguous	0.012	Stabilizing	0.89	D	0.757	deleterious	None	None	None	None	N
K/W	0.7918	likely_pathogenic	0.8431	pathogenic	-0.278	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
K/Y	0.7447	likely_pathogenic	0.789	pathogenic	0.023	Stabilizing	0.968	D	0.763	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.