TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23279	70060;70061;70062	chr2:178576297;178576296;178576295	chr2:179441024;179441023;179441022
N2AB	21638	65137;65138;65139	chr2:178576297;178576296;178576295	chr2:179441024;179441023;179441022
N2A	20711	62356;62357;62358	chr2:178576297;178576296;178576295	chr2:179441024;179441023;179441022
N2B	14214	42865;42866;42867	chr2:178576297;178576296;178576295	chr2:179441024;179441023;179441022
Novex-1	14339	43240;43241;43242	chr2:178576297;178576296;178576295	chr2:179441024;179441023;179441022
Novex-2	14406	43441;43442;43443	chr2:178576297;178576296;178576295	chr2:179441024;179441023;179441022
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-57
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.2175
• 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
H/Q	rs752879532	-1.842	0.97	N	0.689	0.298	0.291694819147	gnomAD-4.0.0	4.15167E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.43019E-06	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
H/A	0.9826	likely_pathogenic	0.9845	pathogenic	-2.351	Highly Destabilizing	0.86	D	0.735	prob.delet.	None	None	None	None	N
H/C	0.6381	likely_pathogenic	0.6229	pathogenic	-1.293	Destabilizing	0.998	D	0.812	deleterious	None	None	None	None	N
H/D	0.9868	likely_pathogenic	0.9898	pathogenic	-2.466	Highly Destabilizing	0.99	D	0.752	deleterious	N	0.518614875	None	None	N
H/E	0.965	likely_pathogenic	0.9717	pathogenic	-2.243	Highly Destabilizing	0.926	D	0.693	prob.neutral	None	None	None	None	N
H/F	0.8973	likely_pathogenic	0.8979	pathogenic	-0.404	Destabilizing	0.754	D	0.725	prob.delet.	None	None	None	None	N
H/G	0.9806	likely_pathogenic	0.9836	pathogenic	-2.76	Highly Destabilizing	0.926	D	0.733	prob.delet.	None	None	None	None	N
H/I	0.965	likely_pathogenic	0.9681	pathogenic	-1.092	Destabilizing	0.956	D	0.792	deleterious	None	None	None	None	N
H/K	0.7163	likely_pathogenic	0.7229	pathogenic	-1.269	Destabilizing	0.978	D	0.734	prob.delet.	None	None	None	None	N
H/L	0.8565	likely_pathogenic	0.8521	pathogenic	-1.092	Destabilizing	0.698	D	0.745	deleterious	N	0.422546978	None	None	N
H/M	0.9647	likely_pathogenic	0.9663	pathogenic	-1.167	Destabilizing	0.998	D	0.791	deleterious	None	None	None	None	N
H/N	0.8677	likely_pathogenic	0.8897	pathogenic	-2.301	Highly Destabilizing	0.904	D	0.716	prob.delet.	N	0.499855756	None	None	N
H/P	0.9914	likely_pathogenic	0.9929	pathogenic	-1.511	Destabilizing	0.99	D	0.79	deleterious	N	0.488812043	None	None	N
H/Q	0.8146	likely_pathogenic	0.8338	pathogenic	-1.936	Destabilizing	0.97	D	0.689	prob.neutral	N	0.466185899	None	None	N
H/R	0.3474	ambiguous	0.3541	ambiguous	-1.224	Destabilizing	0.97	D	0.685	prob.neutral	N	0.409100465	None	None	N
H/S	0.9584	likely_pathogenic	0.9621	pathogenic	-2.46	Highly Destabilizing	0.926	D	0.73	prob.delet.	None	None	None	None	N
H/T	0.9786	likely_pathogenic	0.9804	pathogenic	-2.115	Highly Destabilizing	0.978	D	0.75	deleterious	None	None	None	None	N
H/V	0.9471	likely_pathogenic	0.9506	pathogenic	-1.511	Destabilizing	0.956	D	0.749	deleterious	None	None	None	None	N
H/W	0.7865	likely_pathogenic	0.7637	pathogenic	0.325	Stabilizing	0.994	D	0.789	deleterious	None	None	None	None	N
H/Y	0.4859	ambiguous	0.4706	ambiguous	-0.037	Destabilizing	0.006	N	0.365	neutral	N	0.383945731	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.