TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23557	70894;70895;70896	chr2:178575463;178575462;178575461	chr2:179440190;179440189;179440188
N2AB	21916	65971;65972;65973	chr2:178575463;178575462;178575461	chr2:179440190;179440189;179440188
N2A	20989	63190;63191;63192	chr2:178575463;178575462;178575461	chr2:179440190;179440189;179440188
N2B	14492	43699;43700;43701	chr2:178575463;178575462;178575461	chr2:179440190;179440189;179440188
Novex-1	14617	44074;44075;44076	chr2:178575463;178575462;178575461	chr2:179440190;179440189;179440188
Novex-2	14684	44275;44276;44277	chr2:178575463;178575462;178575461	chr2:179440190;179440189;179440188
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: Fn3-59
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.787
• Predicted PPI site: I

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	0.029	N	0.247	0.113	0.0401082797425	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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	0.2221	likely_benign	0.2348	benign	0.049	Stabilizing	0.031	N	0.272	neutral	None	None	None	None	I
K/C	0.599	likely_pathogenic	0.6115	pathogenic	0.069	Stabilizing	0.864	D	0.213	neutral	None	None	None	None	I
K/D	0.4879	ambiguous	0.5065	ambiguous	-0.061	Destabilizing	None	N	0.131	neutral	None	None	None	None	I
K/E	0.1431	likely_benign	0.1536	benign	-0.048	Destabilizing	None	N	0.075	neutral	N	0.407735028	None	None	I
K/F	0.6938	likely_pathogenic	0.6994	pathogenic	-0.064	Destabilizing	0.214	N	0.299	neutral	None	None	None	None	I
K/G	0.3394	likely_benign	0.3439	ambiguous	-0.169	Destabilizing	0.031	N	0.277	neutral	None	None	None	None	I
K/H	0.3153	likely_benign	0.3223	benign	-0.486	Destabilizing	0.356	N	0.257	neutral	None	None	None	None	I
K/I	0.2277	likely_benign	0.2417	benign	0.556	Stabilizing	0.029	N	0.382	neutral	N	0.475154886	None	None	I
K/L	0.2268	likely_benign	0.2385	benign	0.556	Stabilizing	None	N	0.149	neutral	None	None	None	None	I
K/M	0.2097	likely_benign	0.22	benign	0.291	Stabilizing	0.214	N	0.258	neutral	None	None	None	None	I
K/N	0.4084	ambiguous	0.4168	ambiguous	0.4	Stabilizing	0.029	N	0.247	neutral	N	0.48937219	None	None	I
K/P	0.4885	ambiguous	0.4774	ambiguous	0.415	Stabilizing	0.136	N	0.343	neutral	None	None	None	None	I
K/Q	0.1154	likely_benign	0.1192	benign	0.241	Stabilizing	0.029	N	0.281	neutral	N	0.500781262	None	None	I
K/R	0.0767	likely_benign	0.0773	benign	-0.029	Destabilizing	None	N	0.131	neutral	N	0.481502068	None	None	I
K/S	0.3235	likely_benign	0.3298	benign	-0.004	Destabilizing	0.031	N	0.252	neutral	None	None	None	None	I
K/T	0.1589	likely_benign	0.167	benign	0.15	Stabilizing	0.024	N	0.28	neutral	N	0.472978586	None	None	I
K/V	0.1874	likely_benign	0.2049	benign	0.415	Stabilizing	0.016	N	0.269	neutral	None	None	None	None	I
K/W	0.7098	likely_pathogenic	0.7039	pathogenic	-0.103	Destabilizing	0.864	D	0.211	neutral	None	None	None	None	I
K/Y	0.5904	likely_pathogenic	0.5933	pathogenic	0.223	Stabilizing	0.356	N	0.3	neutral	None	None	None	None	I

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.