TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27282	82069;82070;82071	chr2:178564288;178564287;178564286	chr2:179429015;179429014;179429013
N2AB	25641	77146;77147;77148	chr2:178564288;178564287;178564286	chr2:179429015;179429014;179429013
N2A	24714	74365;74366;74367	chr2:178564288;178564287;178564286	chr2:179429015;179429014;179429013
N2B	18217	54874;54875;54876	chr2:178564288;178564287;178564286	chr2:179429015;179429014;179429013
Novex-1	18342	55249;55250;55251	chr2:178564288;178564287;178564286	chr2:179429015;179429014;179429013
Novex-2	18409	55450;55451;55452	chr2:178564288;178564287;178564286	chr2:179429015;179429014;179429013
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-140
• Domain position: 5
• Structural Position: 8
• Q(SASA): 0.6731
• 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	rs761201021	0.443	0.124	N	0.634	0.153	0.295974979623	gnomAD-2.1.1	2.5E-05	None	None	None	None	N	None	0	0	None	0	1.53846E-04	None	0	None	0	3.13E-05	0
K/E	rs761201021	0.443	0.124	N	0.634	0.153	0.295974979623	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	2.94E-05	0	4.78927E-04
K/E	rs761201021	0.443	0.124	N	0.634	0.153	0.295974979623	gnomAD-4.0.0	4.09071E-05	None	None	None	None	N	None	0	3.33367E-05	None	0	8.91703E-05	None	0	1.6442E-04	4.40765E-05	1.09791E-05	9.60707E-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	0.3828	ambiguous	0.3649	ambiguous	0.066	Stabilizing	0.272	N	0.605	neutral	None	None	None	None	N
K/C	0.7231	likely_pathogenic	0.7078	pathogenic	-0.257	Destabilizing	0.968	D	0.717	prob.delet.	None	None	None	None	N
K/D	0.655	likely_pathogenic	0.6331	pathogenic	-0.102	Destabilizing	0.567	D	0.625	neutral	None	None	None	None	N
K/E	0.2281	likely_benign	0.1914	benign	-0.106	Destabilizing	0.124	N	0.634	neutral	N	0.505928871	None	None	N
K/F	0.8561	likely_pathogenic	0.8464	pathogenic	-0.213	Destabilizing	0.726	D	0.679	prob.neutral	None	None	None	None	N
K/G	0.4107	ambiguous	0.3539	ambiguous	-0.096	Destabilizing	0.272	N	0.587	neutral	None	None	None	None	N
K/H	0.3407	ambiguous	0.3182	benign	-0.279	Destabilizing	0.909	D	0.641	neutral	None	None	None	None	N
K/I	0.5109	ambiguous	0.5014	ambiguous	0.411	Stabilizing	0.667	D	0.691	prob.neutral	N	0.485074127	None	None	N
K/L	0.4505	ambiguous	0.4252	ambiguous	0.411	Stabilizing	0.272	N	0.587	neutral	None	None	None	None	N
K/M	0.3275	likely_benign	0.3213	benign	0.097	Stabilizing	0.968	D	0.641	neutral	None	None	None	None	N
K/N	0.524	ambiguous	0.4919	ambiguous	0.179	Stabilizing	0.497	N	0.592	neutral	D	0.531576677	None	None	N
K/P	0.7948	likely_pathogenic	0.7858	pathogenic	0.322	Stabilizing	0.726	D	0.661	neutral	None	None	None	None	N
K/Q	0.1506	likely_benign	0.1311	benign	0.028	Stabilizing	0.025	N	0.263	neutral	N	0.508102385	None	None	N
K/R	0.0757	likely_benign	0.0686	benign	-0.03	Destabilizing	0.001	N	0.207	neutral	N	0.436220857	None	None	N
K/S	0.4411	ambiguous	0.4013	ambiguous	-0.227	Destabilizing	0.272	N	0.599	neutral	None	None	None	None	N
K/T	0.2119	likely_benign	0.212	benign	-0.101	Destabilizing	0.497	N	0.624	neutral	N	0.520532964	None	None	N
K/V	0.4548	ambiguous	0.4539	ambiguous	0.322	Stabilizing	0.567	D	0.641	neutral	None	None	None	None	N
K/W	0.7613	likely_pathogenic	0.7085	pathogenic	-0.292	Destabilizing	0.968	D	0.705	prob.neutral	None	None	None	None	N
K/Y	0.7166	likely_pathogenic	0.6973	pathogenic	0.067	Stabilizing	0.726	D	0.693	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.