TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22803	68632;68633;68634	chr2:178578108;178578107;178578106	chr2:179442835;179442834;179442833
N2AB	21162	63709;63710;63711	chr2:178578108;178578107;178578106	chr2:179442835;179442834;179442833
N2A	20235	60928;60929;60930	chr2:178578108;178578107;178578106	chr2:179442835;179442834;179442833
N2B	13738	41437;41438;41439	chr2:178578108;178578107;178578106	chr2:179442835;179442834;179442833
Novex-1	13863	41812;41813;41814	chr2:178578108;178578107;178578106	chr2:179442835;179442834;179442833
Novex-2	13930	42013;42014;42015	chr2:178578108;178578107;178578106	chr2:179442835;179442834;179442833
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Fn3-53
• Domain position: 61
• Structural Position: 91
• Q(SASA): 0.1863
• Predicted PPI site: I

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
F/L	None	None	0.309	N	0.473	0.304	0.369867359543	gnomAD-4.0.0	6.84414E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	1.65711E-05
F/V	None	None	0.684	N	0.493	0.377	0.617576649361	gnomAD-4.0.0	2.05323E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79934E-06	0	1.65706E-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
F/A	0.6909	likely_pathogenic	0.67	pathogenic	-2.278	Highly Destabilizing	0.373	N	0.522	neutral	None	None	None	None	I
F/C	0.281	likely_benign	0.248	benign	-1.584	Destabilizing	0.003	N	0.438	neutral	N	0.502320058	None	None	I
F/D	0.9438	likely_pathogenic	0.9379	pathogenic	-1.72	Destabilizing	0.984	D	0.599	neutral	None	None	None	None	I
F/E	0.938	likely_pathogenic	0.9357	pathogenic	-1.562	Destabilizing	0.953	D	0.612	neutral	None	None	None	None	I
F/G	0.8309	likely_pathogenic	0.8167	pathogenic	-2.669	Highly Destabilizing	0.854	D	0.577	neutral	None	None	None	None	I
F/H	0.6142	likely_pathogenic	0.5906	pathogenic	-0.959	Destabilizing	0.91	D	0.553	neutral	None	None	None	None	I
F/I	0.3854	ambiguous	0.337	benign	-1.058	Destabilizing	0.684	D	0.435	neutral	N	0.467507671	None	None	I
F/K	0.925	likely_pathogenic	0.9237	pathogenic	-1.807	Destabilizing	0.953	D	0.617	neutral	None	None	None	None	I
F/L	0.8428	likely_pathogenic	0.806	pathogenic	-1.058	Destabilizing	0.309	N	0.473	neutral	N	0.506165652	None	None	I
F/M	0.488	ambiguous	0.4704	ambiguous	-0.871	Destabilizing	0.984	D	0.519	neutral	None	None	None	None	I
F/N	0.8038	likely_pathogenic	0.78	pathogenic	-2.145	Highly Destabilizing	0.953	D	0.609	neutral	None	None	None	None	I
F/P	0.9966	likely_pathogenic	0.9958	pathogenic	-1.465	Destabilizing	0.984	D	0.619	neutral	None	None	None	None	I
F/Q	0.8321	likely_pathogenic	0.8113	pathogenic	-2.086	Highly Destabilizing	0.953	D	0.625	neutral	None	None	None	None	I
F/R	0.8549	likely_pathogenic	0.8546	pathogenic	-1.29	Destabilizing	0.953	D	0.608	neutral	None	None	None	None	I
F/S	0.6143	likely_pathogenic	0.5683	pathogenic	-2.874	Highly Destabilizing	0.684	D	0.565	neutral	N	0.490513451	None	None	I
F/T	0.6688	likely_pathogenic	0.6374	pathogenic	-2.607	Highly Destabilizing	0.742	D	0.569	neutral	None	None	None	None	I
F/V	0.3308	likely_benign	0.2962	benign	-1.465	Destabilizing	0.684	D	0.493	neutral	N	0.515051708	None	None	I
F/W	0.5831	likely_pathogenic	0.5594	ambiguous	-0.138	Destabilizing	0.953	D	0.517	neutral	None	None	None	None	I
F/Y	0.1496	likely_benign	0.1398	benign	-0.467	Destabilizing	0.003	N	0.171	neutral	N	0.427760797	None	None	I

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.