TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4012	12259;12260;12261	chr2:178741199;178741198;178741197	chr2:179605926;179605925;179605924
N2AB	3695	11308;11309;11310	chr2:178741199;178741198;178741197	chr2:179605926;179605925;179605924
N2A	None	None	chr2:None	chr2:None
N2B	3649	11170;11171;11172	chr2:178741199;178741198;178741197	chr2:179605926;179605925;179605924
Novex-1	3774	11545;11546;11547	chr2:178741199;178741198;178741197	chr2:179605926;179605925;179605924
Novex-2	3841	11746;11747;11748	chr2:178741199;178741198;178741197	chr2:179605926;179605925;179605924
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-28
• Domain position: 75
• Structural Position: 157
• Q(SASA): 0.2098
• 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	rs763904872	-1.054	0.117	D	0.545	0.16	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
K/N	rs763904872	-1.054	0.117	D	0.545	0.16	None	gnomAD-4.0.0	1.59246E-06	None	None	None	None	N	None	0	2.28666E-05	None	0	0	None	0	0	0	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	0.7199	likely_pathogenic	0.6161	pathogenic	-1.025	Destabilizing	0.035	N	0.543	neutral	None	None	None	None	N
K/C	0.843	likely_pathogenic	0.7875	pathogenic	-1.348	Destabilizing	0.935	D	0.733	prob.delet.	None	None	None	None	N
K/D	0.9421	likely_pathogenic	0.8873	pathogenic	-0.92	Destabilizing	0.149	N	0.593	neutral	None	None	None	None	N
K/E	0.3657	ambiguous	0.2777	benign	-0.754	Destabilizing	0.062	N	0.569	neutral	N	0.494905317	None	None	N
K/F	0.9136	likely_pathogenic	0.8695	pathogenic	-0.695	Destabilizing	0.555	D	0.745	deleterious	None	None	None	None	N
K/G	0.8632	likely_pathogenic	0.7868	pathogenic	-1.418	Destabilizing	0.149	N	0.645	neutral	None	None	None	None	N
K/H	0.4947	ambiguous	0.4137	ambiguous	-1.702	Destabilizing	0.555	D	0.627	neutral	None	None	None	None	N
K/I	0.5294	ambiguous	0.439	ambiguous	0.024	Stabilizing	0.317	N	0.731	prob.delet.	N	0.500298471	None	None	N
K/L	0.6182	likely_pathogenic	0.5251	ambiguous	0.024	Stabilizing	0.081	N	0.639	neutral	None	None	None	None	N
K/M	0.4034	ambiguous	0.3294	benign	-0.155	Destabilizing	0.935	D	0.623	neutral	None	None	None	None	N
K/N	0.7996	likely_pathogenic	0.7062	pathogenic	-1.113	Destabilizing	0.117	N	0.545	neutral	D	0.541911499	None	None	N
K/P	0.993	likely_pathogenic	0.9853	pathogenic	-0.298	Destabilizing	0.555	D	0.612	neutral	None	None	None	None	N
K/Q	0.2261	likely_benign	0.1887	benign	-1.145	Destabilizing	0.117	N	0.581	neutral	N	0.511665423	None	None	N
K/R	0.0989	likely_benign	0.0895	benign	-0.872	Destabilizing	None	N	0.247	neutral	N	0.47264359	None	None	N
K/S	0.7698	likely_pathogenic	0.6787	pathogenic	-1.788	Destabilizing	0.081	N	0.552	neutral	None	None	None	None	N
K/T	0.3549	ambiguous	0.2826	benign	-1.398	Destabilizing	0.002	N	0.441	neutral	N	0.485283203	None	None	N
K/V	0.519	ambiguous	0.4287	ambiguous	-0.298	Destabilizing	0.081	N	0.665	neutral	None	None	None	None	N
K/W	0.9083	likely_pathogenic	0.8643	pathogenic	-0.584	Destabilizing	0.935	D	0.752	deleterious	None	None	None	None	N
K/Y	0.8388	likely_pathogenic	0.7731	pathogenic	-0.227	Destabilizing	0.555	D	0.717	prob.delet.	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.