TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15885	47878;47879;47880	chr2:178617432;178617431;178617430	chr2:179482159;179482158;179482157
N2AB	14244	42955;42956;42957	chr2:178617432;178617431;178617430	chr2:179482159;179482158;179482157
N2A	13317	40174;40175;40176	chr2:178617432;178617431;178617430	chr2:179482159;179482158;179482157
N2B	6820	20683;20684;20685	chr2:178617432;178617431;178617430	chr2:179482159;179482158;179482157
Novex-1	6945	21058;21059;21060	chr2:178617432;178617431;178617430	chr2:179482159;179482158;179482157
Novex-2	7012	21259;21260;21261	chr2:178617432;178617431;178617430	chr2:179482159;179482158;179482157
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: Fn3-3
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.2961
• 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	0.012	N	0.121	0.129	0.173771789658	gnomAD-4.0.0	1.63879E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.09023E-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	0.3873	ambiguous	0.3937	ambiguous	0.009	Stabilizing	0.525	D	0.369	neutral	None	None	None	None	N
K/C	0.6974	likely_pathogenic	0.6734	pathogenic	-0.177	Destabilizing	0.998	D	0.327	neutral	None	None	None	None	N
K/D	0.5956	likely_pathogenic	0.5828	pathogenic	0.101	Stabilizing	0.525	D	0.351	neutral	None	None	None	None	N
K/E	0.2097	likely_benign	0.2062	benign	0.103	Stabilizing	0.012	N	0.121	neutral	N	0.43193958	None	None	N
K/F	0.7511	likely_pathogenic	0.7238	pathogenic	-0.238	Destabilizing	0.991	D	0.361	neutral	None	None	None	None	N
K/G	0.5421	ambiguous	0.5456	ambiguous	-0.183	Destabilizing	0.688	D	0.381	neutral	None	None	None	None	N
K/H	0.2872	likely_benign	0.2553	benign	-0.498	Destabilizing	0.974	D	0.349	neutral	None	None	None	None	N
K/I	0.4202	ambiguous	0.4188	ambiguous	0.433	Stabilizing	0.934	D	0.387	neutral	N	0.452738982	None	None	N
K/L	0.3946	ambiguous	0.3916	ambiguous	0.433	Stabilizing	0.842	D	0.431	neutral	None	None	None	None	N
K/M	0.2562	likely_benign	0.2568	benign	0.267	Stabilizing	0.991	D	0.34	neutral	None	None	None	None	N
K/N	0.4029	ambiguous	0.4091	ambiguous	0.253	Stabilizing	0.051	N	0.156	neutral	N	0.428908365	None	None	N
K/P	0.9392	likely_pathogenic	0.9328	pathogenic	0.32	Stabilizing	0.915	D	0.398	neutral	None	None	None	None	N
K/Q	0.1432	likely_benign	0.1358	benign	0.071	Stabilizing	0.669	D	0.36	neutral	N	0.447919158	None	None	N
K/R	0.0881	likely_benign	0.0879	benign	-0.03	Destabilizing	0.801	D	0.341	neutral	N	0.442148701	None	None	N
K/S	0.3947	ambiguous	0.3904	ambiguous	-0.237	Destabilizing	0.08	N	0.097	neutral	None	None	None	None	N
K/T	0.1963	likely_benign	0.1942	benign	-0.088	Destabilizing	0.051	N	0.201	neutral	N	0.445355088	None	None	N
K/V	0.362	ambiguous	0.3645	ambiguous	0.32	Stabilizing	0.842	D	0.411	neutral	None	None	None	None	N
K/W	0.7685	likely_pathogenic	0.7237	pathogenic	-0.255	Destabilizing	0.998	D	0.39	neutral	None	None	None	None	N
K/Y	0.5786	likely_pathogenic	0.5187	ambiguous	0.108	Stabilizing	0.991	D	0.371	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.