TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26248	78967;78968;78969	chr2:178567390;178567389;178567388	chr2:179432117;179432116;179432115
N2AB	24607	74044;74045;74046	chr2:178567390;178567389;178567388	chr2:179432117;179432116;179432115
N2A	23680	71263;71264;71265	chr2:178567390;178567389;178567388	chr2:179432117;179432116;179432115
N2B	17183	51772;51773;51774	chr2:178567390;178567389;178567388	chr2:179432117;179432116;179432115
Novex-1	17308	52147;52148;52149	chr2:178567390;178567389;178567388	chr2:179432117;179432116;179432115
Novex-2	17375	52348;52349;52350	chr2:178567390;178567389;178567388	chr2:179432117;179432116;179432115
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-137
• Domain position: 56
• Structural Position: 135
• Q(SASA): 0.3262
• 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/Q	rs1281337813	-0.587	0.901	N	0.579	0.309	0.281780670237	gnomAD-2.1.1	4.23E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.23E-06	0
K/Q	rs1281337813	-0.587	0.901	N	0.579	0.309	0.281780670237	gnomAD-4.0.0	2.76372E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.71282E-06	0	1.67527E-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	0.3673	ambiguous	0.2859	benign	-0.435	Destabilizing	0.415	N	0.589	neutral	None	None	None	None	N
K/C	0.5888	likely_pathogenic	0.4966	ambiguous	-0.461	Destabilizing	0.996	D	0.754	deleterious	None	None	None	None	N
K/D	0.6792	likely_pathogenic	0.5888	pathogenic	-0.315	Destabilizing	0.923	D	0.651	neutral	None	None	None	None	N
K/E	0.2477	likely_benign	0.2078	benign	-0.224	Destabilizing	0.722	D	0.495	neutral	N	0.471893655	None	None	N
K/F	0.7666	likely_pathogenic	0.6709	pathogenic	-0.227	Destabilizing	0.961	D	0.748	deleterious	None	None	None	None	N
K/G	0.5486	ambiguous	0.4562	ambiguous	-0.792	Destabilizing	0.633	D	0.639	neutral	None	None	None	None	N
K/H	0.2084	likely_benign	0.1725	benign	-1.257	Destabilizing	0.989	D	0.701	prob.neutral	None	None	None	None	N
K/I	0.4434	ambiguous	0.3632	ambiguous	0.482	Stabilizing	0.961	D	0.755	deleterious	None	None	None	None	N
K/L	0.3971	ambiguous	0.3248	benign	0.482	Stabilizing	0.775	D	0.653	neutral	None	None	None	None	N
K/M	0.2644	likely_benign	0.2167	benign	0.463	Stabilizing	0.995	D	0.693	prob.neutral	N	0.507278452	None	None	N
K/N	0.4455	ambiguous	0.3637	ambiguous	-0.432	Destabilizing	0.722	D	0.549	neutral	N	0.456964275	None	None	N
K/P	0.9512	likely_pathogenic	0.9396	pathogenic	0.208	Stabilizing	0.961	D	0.705	prob.neutral	None	None	None	None	N
K/Q	0.1228	likely_benign	0.1061	benign	-0.553	Destabilizing	0.901	D	0.579	neutral	N	0.478224982	None	None	N
K/R	0.0791	likely_benign	0.0743	benign	-0.626	Destabilizing	0.018	N	0.257	neutral	N	0.435607568	None	None	N
K/S	0.3402	ambiguous	0.2602	benign	-1.024	Destabilizing	0.044	N	0.206	neutral	None	None	None	None	N
K/T	0.1532	likely_benign	0.1171	benign	-0.736	Destabilizing	0.565	D	0.619	neutral	N	0.429777674	None	None	N
K/V	0.3799	ambiguous	0.3061	benign	0.208	Stabilizing	0.923	D	0.657	neutral	None	None	None	None	N
K/W	0.78	likely_pathogenic	0.6982	pathogenic	-0.138	Destabilizing	0.996	D	0.739	prob.delet.	None	None	None	None	N
K/Y	0.6145	likely_pathogenic	0.5214	ambiguous	0.182	Stabilizing	0.987	D	0.735	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.