TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7396	22411;22412;22413	chr2:178722713;178722712;178722711	chr2:179587440;179587439;179587438
N2AB	7079	21460;21461;21462	chr2:178722713;178722712;178722711	chr2:179587440;179587439;179587438
N2A	6152	18679;18680;18681	chr2:178722713;178722712;178722711	chr2:179587440;179587439;179587438
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-58
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.304
• 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	0.066	N	0.49	0.105	0.0884992946249	gnomAD-4.0.0	3.18563E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86845E-05	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	0.3231	likely_benign	0.4363	ambiguous	-0.939	Destabilizing	0.115	N	0.471	neutral	None	None	None	None	N
K/C	0.6306	likely_pathogenic	0.7025	pathogenic	-1.184	Destabilizing	0.944	D	0.585	neutral	None	None	None	None	N
K/D	0.7184	likely_pathogenic	0.8403	pathogenic	-0.767	Destabilizing	0.385	N	0.573	neutral	None	None	None	None	N
K/E	0.1665	likely_benign	0.2469	benign	-0.636	Destabilizing	0.066	N	0.49	neutral	N	0.444632483	None	None	N
K/F	0.6001	likely_pathogenic	0.7191	pathogenic	-0.759	Destabilizing	0.467	N	0.619	neutral	None	None	None	None	N
K/G	0.5994	likely_pathogenic	0.7391	pathogenic	-1.301	Destabilizing	0.385	N	0.585	neutral	None	None	None	None	N
K/H	0.2818	likely_benign	0.3316	benign	-1.643	Destabilizing	0.649	D	0.569	neutral	None	None	None	None	N
K/I	0.1317	likely_benign	0.1751	benign	0.012	Stabilizing	None	N	0.565	neutral	N	0.488770049	None	None	N
K/L	0.2356	likely_benign	0.2984	benign	0.012	Stabilizing	0.001	N	0.553	neutral	None	None	None	None	N
K/M	0.1316	likely_benign	0.1595	benign	-0.039	Destabilizing	0.005	N	0.457	neutral	None	None	None	None	N
K/N	0.4627	ambiguous	0.607	pathogenic	-0.905	Destabilizing	0.321	N	0.55	neutral	N	0.52172783	None	None	N
K/P	0.97	likely_pathogenic	0.9873	pathogenic	-0.277	Destabilizing	0.817	D	0.599	neutral	None	None	None	None	N
K/Q	0.1229	likely_benign	0.1474	benign	-1.032	Destabilizing	0.002	N	0.34	neutral	N	0.496829385	None	None	N
K/R	0.0779	likely_benign	0.0845	benign	-0.737	Destabilizing	0.042	N	0.515	neutral	N	0.483150799	None	None	N
K/S	0.4178	ambiguous	0.5469	ambiguous	-1.59	Destabilizing	0.024	N	0.322	neutral	None	None	None	None	N
K/T	0.1265	likely_benign	0.1631	benign	-1.247	Destabilizing	None	N	0.361	neutral	N	0.43899459	None	None	N
K/V	0.1264	likely_benign	0.1729	benign	-0.277	Destabilizing	None	N	0.531	neutral	None	None	None	None	N
K/W	0.6879	likely_pathogenic	0.774	pathogenic	-0.622	Destabilizing	0.987	D	0.605	neutral	None	None	None	None	N
K/Y	0.5423	ambiguous	0.6324	pathogenic	-0.265	Destabilizing	0.172	N	0.612	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.