TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2255	6988;6989;6990	chr2:178774948;178774947;178774946	chr2:179639675;179639674;179639673
N2AB	2255	6988;6989;6990	chr2:178774948;178774947;178774946	chr2:179639675;179639674;179639673
N2A	2255	6988;6989;6990	chr2:178774948;178774947;178774946	chr2:179639675;179639674;179639673
N2B	2209	6850;6851;6852	chr2:178774948;178774947;178774946	chr2:179639675;179639674;179639673
Novex-1	2209	6850;6851;6852	chr2:178774948;178774947;178774946	chr2:179639675;179639674;179639673
Novex-2	2209	6850;6851;6852	chr2:178774948;178774947;178774946	chr2:179639675;179639674;179639673
Novex-3	2255	6988;6989;6990	chr2:178774948;178774947;178774946	chr2:179639675;179639674;179639673

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-11
• Domain position: 82
• Structural Position: 168
• Q(SASA): 0.5416
• 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/N	None	None	0.722	N	0.579	0.174	0.236890367714	gnomAD-4.0.0	3.43349E-06	None	None	None	None	N	None	0	0	None	0	2.55872E-05	None	1.91549E-05	0	9.01554E-07	0	3.33356E-05
K/R	None	None	0.003	N	0.257	0.114	0.282179105231	gnomAD-4.0.0	1.59126E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85753E-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	0.3404	ambiguous	0.3733	ambiguous	-0.4	Destabilizing	0.775	D	0.648	neutral	None	None	None	None	N
K/C	0.5953	likely_pathogenic	0.598	pathogenic	-0.469	Destabilizing	0.996	D	0.695	prob.neutral	None	None	None	None	N
K/D	0.7467	likely_pathogenic	0.7708	pathogenic	0.312	Stabilizing	0.923	D	0.665	neutral	None	None	None	None	N
K/E	0.1815	likely_benign	0.2039	benign	0.387	Stabilizing	0.722	D	0.636	neutral	N	0.501858914	None	None	N
K/F	0.6832	likely_pathogenic	0.7084	pathogenic	-0.291	Destabilizing	0.987	D	0.688	prob.neutral	None	None	None	None	N
K/G	0.5208	ambiguous	0.5548	ambiguous	-0.705	Destabilizing	0.775	D	0.599	neutral	None	None	None	None	N
K/H	0.2496	likely_benign	0.2518	benign	-0.979	Destabilizing	0.961	D	0.681	prob.neutral	None	None	None	None	N
K/I	0.3402	ambiguous	0.3672	ambiguous	0.36	Stabilizing	0.949	D	0.688	prob.neutral	D	0.545835267	None	None	N
K/L	0.3422	ambiguous	0.362	ambiguous	0.36	Stabilizing	0.775	D	0.599	neutral	None	None	None	None	N
K/M	0.2055	likely_benign	0.2209	benign	0.175	Stabilizing	0.996	D	0.659	neutral	None	None	None	None	N
K/N	0.4711	ambiguous	0.5009	ambiguous	-0.087	Destabilizing	0.722	D	0.579	neutral	N	0.509191112	None	None	N
K/P	0.8983	likely_pathogenic	0.9126	pathogenic	0.137	Stabilizing	0.961	D	0.697	prob.neutral	None	None	None	None	N
K/Q	0.1091	likely_benign	0.1144	benign	-0.196	Destabilizing	0.722	D	0.61	neutral	N	0.509237744	None	None	N
K/R	0.0749	likely_benign	0.0751	benign	-0.263	Destabilizing	0.003	N	0.257	neutral	N	0.474892086	None	None	N
K/S	0.3724	ambiguous	0.3999	ambiguous	-0.774	Destabilizing	0.775	D	0.563	neutral	None	None	None	None	N
K/T	0.15	likely_benign	0.1633	benign	-0.503	Destabilizing	0.722	D	0.633	neutral	N	0.48390903	None	None	N
K/V	0.3089	likely_benign	0.3273	benign	0.137	Stabilizing	0.923	D	0.629	neutral	None	None	None	None	N
K/W	0.695	likely_pathogenic	0.7196	pathogenic	-0.171	Destabilizing	0.996	D	0.691	prob.neutral	None	None	None	None	N
K/Y	0.5647	likely_pathogenic	0.5883	pathogenic	0.14	Stabilizing	0.987	D	0.694	prob.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.