TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18040	54343;54344;54345	chr2:178605059;178605058;178605057	chr2:179469786;179469785;179469784
N2AB	16399	49420;49421;49422	chr2:178605059;178605058;178605057	chr2:179469786;179469785;179469784
N2A	15472	46639;46640;46641	chr2:178605059;178605058;178605057	chr2:179469786;179469785;179469784
N2B	8975	27148;27149;27150	chr2:178605059;178605058;178605057	chr2:179469786;179469785;179469784
Novex-1	9100	27523;27524;27525	chr2:178605059;178605058;178605057	chr2:179469786;179469785;179469784
Novex-2	9167	27724;27725;27726	chr2:178605059;178605058;178605057	chr2:179469786;179469785;179469784
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: Ig-114
• Domain position: 73
• Structural Position: 151
• Q(SASA): 0.4574
• 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	rs1465644822	0.013	0.959	N	0.488	0.221	0.350964488264	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
K/E	rs1465644822	0.013	0.959	N	0.488	0.221	0.350964488264	gnomAD-4.0.0	1.36952E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80004E-06	0	0
K/R	None	None	0.03	N	0.106	0.128	0.267299060538	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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	0.3629	ambiguous	0.4058	ambiguous	-0.516	Destabilizing	0.927	D	0.476	neutral	None	None	None	None	N
K/C	0.6697	likely_pathogenic	0.7407	pathogenic	-0.49	Destabilizing	1.0	D	0.547	neutral	None	None	None	None	N
K/D	0.7756	likely_pathogenic	0.7969	pathogenic	-0.307	Destabilizing	0.984	D	0.567	neutral	None	None	None	None	N
K/E	0.3217	likely_benign	0.3235	benign	-0.205	Destabilizing	0.959	D	0.488	neutral	N	0.414749506	None	None	N
K/F	0.864	likely_pathogenic	0.8866	pathogenic	-0.164	Destabilizing	0.999	D	0.567	neutral	None	None	None	None	N
K/G	0.435	ambiguous	0.4731	ambiguous	-0.89	Destabilizing	0.088	N	0.306	neutral	None	None	None	None	N
K/H	0.4064	ambiguous	0.4438	ambiguous	-1.277	Destabilizing	0.999	D	0.565	neutral	None	None	None	None	N
K/I	0.5472	ambiguous	0.6352	pathogenic	0.453	Stabilizing	0.988	D	0.6	neutral	N	0.469490855	None	None	N
K/L	0.5289	ambiguous	0.59	pathogenic	0.453	Stabilizing	0.969	D	0.533	neutral	None	None	None	None	N
K/M	0.3236	likely_benign	0.3596	ambiguous	0.385	Stabilizing	1.0	D	0.558	neutral	None	None	None	None	N
K/N	0.5729	likely_pathogenic	0.6154	pathogenic	-0.492	Destabilizing	0.979	D	0.507	neutral	N	0.457927067	None	None	N
K/P	0.925	likely_pathogenic	0.9308	pathogenic	0.16	Stabilizing	0.999	D	0.621	neutral	None	None	None	None	N
K/Q	0.1843	likely_benign	0.1989	benign	-0.58	Destabilizing	0.959	D	0.518	neutral	N	0.449768944	None	None	N
K/R	0.0853	likely_benign	0.0893	benign	-0.721	Destabilizing	0.03	N	0.106	neutral	N	0.418427317	None	None	N
K/S	0.4401	ambiguous	0.4796	ambiguous	-1.097	Destabilizing	0.864	D	0.485	neutral	None	None	None	None	N
K/T	0.1694	likely_benign	0.1983	benign	-0.794	Destabilizing	0.238	N	0.257	neutral	N	0.400033557	None	None	N
K/V	0.4568	ambiguous	0.5468	ambiguous	0.16	Stabilizing	0.969	D	0.564	neutral	None	None	None	None	N
K/W	0.8712	likely_pathogenic	0.8864	pathogenic	-0.055	Destabilizing	1.0	D	0.563	neutral	None	None	None	None	N
K/Y	0.7665	likely_pathogenic	0.792	pathogenic	0.222	Stabilizing	0.999	D	0.583	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.