TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22784	68575;68576;68577	chr2:178578165;178578164;178578163	chr2:179442892;179442891;179442890
N2AB	21143	63652;63653;63654	chr2:178578165;178578164;178578163	chr2:179442892;179442891;179442890
N2A	20216	60871;60872;60873	chr2:178578165;178578164;178578163	chr2:179442892;179442891;179442890
N2B	13719	41380;41381;41382	chr2:178578165;178578164;178578163	chr2:179442892;179442891;179442890
Novex-1	13844	41755;41756;41757	chr2:178578165;178578164;178578163	chr2:179442892;179442891;179442890
Novex-2	13911	41956;41957;41958	chr2:178578165;178578164;178578163	chr2:179442892;179442891;179442890
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-53
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.2535
• 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
E/K	rs1423648586	-0.262	0.992	N	0.515	0.376	0.373173300195	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
E/K	rs1423648586	-0.262	0.992	N	0.515	0.376	0.373173300195	gnomAD-4.0.0	1.59477E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43476E-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
E/A	0.8431	likely_pathogenic	0.893	pathogenic	-0.754	Destabilizing	0.996	D	0.581	neutral	N	0.488209273	None	None	N
E/C	0.9916	likely_pathogenic	0.9935	pathogenic	-0.459	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
E/D	0.4237	ambiguous	0.4887	ambiguous	-1.425	Destabilizing	0.275	N	0.212	neutral	N	0.479771272	None	None	N
E/F	0.9951	likely_pathogenic	0.9969	pathogenic	-0.015	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
E/G	0.8268	likely_pathogenic	0.8604	pathogenic	-1.204	Destabilizing	0.998	D	0.653	neutral	N	0.487412806	None	None	N
E/H	0.9785	likely_pathogenic	0.987	pathogenic	-0.402	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
E/I	0.9786	likely_pathogenic	0.987	pathogenic	0.502	Stabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
E/K	0.9312	likely_pathogenic	0.9567	pathogenic	-0.801	Destabilizing	0.992	D	0.515	neutral	N	0.515902643	None	None	N
E/L	0.9615	likely_pathogenic	0.9745	pathogenic	0.502	Stabilizing	0.999	D	0.788	deleterious	None	None	None	None	N
E/M	0.9692	likely_pathogenic	0.9794	pathogenic	1.067	Stabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
E/N	0.9229	likely_pathogenic	0.9471	pathogenic	-1.403	Destabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	N
E/P	0.9553	likely_pathogenic	0.9668	pathogenic	0.106	Stabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/Q	0.7769	likely_pathogenic	0.8584	pathogenic	-1.158	Destabilizing	0.999	D	0.646	neutral	N	0.484624421	None	None	N
E/R	0.9476	likely_pathogenic	0.9644	pathogenic	-0.57	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
E/S	0.9001	likely_pathogenic	0.9297	pathogenic	-1.812	Destabilizing	0.994	D	0.563	neutral	None	None	None	None	N
E/T	0.9622	likely_pathogenic	0.9753	pathogenic	-1.418	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
E/V	0.935	likely_pathogenic	0.9577	pathogenic	0.106	Stabilizing	1.0	D	0.768	deleterious	N	0.483133618	None	None	N
E/W	0.9974	likely_pathogenic	0.9984	pathogenic	0.183	Stabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/Y	0.9872	likely_pathogenic	0.992	pathogenic	0.24	Stabilizing	1.0	D	0.769	deleterious	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.