TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19891	59896;59897;59898	chr2:178592233;178592232;178592231	chr2:179456960;179456959;179456958
N2AB	18250	54973;54974;54975	chr2:178592233;178592232;178592231	chr2:179456960;179456959;179456958
N2A	17323	52192;52193;52194	chr2:178592233;178592232;178592231	chr2:179456960;179456959;179456958
N2B	10826	32701;32702;32703	chr2:178592233;178592232;178592231	chr2:179456960;179456959;179456958
Novex-1	10951	33076;33077;33078	chr2:178592233;178592232;178592231	chr2:179456960;179456959;179456958
Novex-2	11018	33277;33278;33279	chr2:178592233;178592232;178592231	chr2:179456960;179456959;179456958
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: Fn3-32
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.3787
• 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	rs2050371739	None	0.625	N	0.331	0.227	0.250579442822	gnomAD-4.0.0	3.19297E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.73069E-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	0.3964	ambiguous	0.3002	benign	-0.469	Destabilizing	0.525	D	0.419	neutral	None	None	None	None	N
K/C	0.6931	likely_pathogenic	0.6034	pathogenic	-0.639	Destabilizing	0.998	D	0.494	neutral	None	None	None	None	N
K/D	0.8319	likely_pathogenic	0.7079	pathogenic	-0.574	Destabilizing	0.842	D	0.389	neutral	None	None	None	None	N
K/E	0.401	ambiguous	0.2766	benign	-0.513	Destabilizing	0.625	D	0.331	neutral	N	0.466703187	None	None	N
K/F	0.9205	likely_pathogenic	0.8486	pathogenic	-0.505	Destabilizing	0.991	D	0.5	neutral	None	None	None	None	N
K/G	0.5011	ambiguous	0.3802	ambiguous	-0.78	Destabilizing	0.728	D	0.413	neutral	None	None	None	None	N
K/H	0.4561	ambiguous	0.3724	ambiguous	-1.258	Destabilizing	0.974	D	0.401	neutral	None	None	None	None	N
K/I	0.6469	likely_pathogenic	0.4994	ambiguous	0.31	Stabilizing	0.966	D	0.511	neutral	N	0.496487705	None	None	N
K/L	0.6498	likely_pathogenic	0.5049	ambiguous	0.31	Stabilizing	0.842	D	0.41	neutral	None	None	None	None	N
K/M	0.4095	ambiguous	0.2901	benign	0.388	Stabilizing	0.991	D	0.393	neutral	None	None	None	None	N
K/N	0.6338	likely_pathogenic	0.4738	ambiguous	-0.504	Destabilizing	0.801	D	0.279	neutral	N	0.48981212	None	None	N
K/P	0.8234	likely_pathogenic	0.7363	pathogenic	0.081	Stabilizing	0.974	D	0.417	neutral	None	None	None	None	N
K/Q	0.2022	likely_benign	0.1632	benign	-0.74	Destabilizing	0.801	D	0.409	neutral	N	0.506936444	None	None	N
K/R	0.0834	likely_benign	0.0803	benign	-0.547	Destabilizing	0.012	N	0.241	neutral	N	0.472458511	None	None	N
K/S	0.4409	ambiguous	0.3198	benign	-1.078	Destabilizing	0.029	N	0.091	neutral	None	None	None	None	N
K/T	0.3275	likely_benign	0.2182	benign	-0.837	Destabilizing	0.669	D	0.338	neutral	N	0.503394706	None	None	N
K/V	0.5802	likely_pathogenic	0.4519	ambiguous	0.081	Stabilizing	0.842	D	0.449	neutral	None	None	None	None	N
K/W	0.8714	likely_pathogenic	0.7844	pathogenic	-0.409	Destabilizing	0.998	D	0.631	neutral	None	None	None	None	N
K/Y	0.8109	likely_pathogenic	0.7038	pathogenic	-0.045	Destabilizing	0.991	D	0.475	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.