TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32321	97186;97187;97188	chr2:178542893;178542892;178542891	chr2:179407620;179407619;179407618
N2AB	30680	92263;92264;92265	chr2:178542893;178542892;178542891	chr2:179407620;179407619;179407618
N2A	29753	89482;89483;89484	chr2:178542893;178542892;178542891	chr2:179407620;179407619;179407618
N2B	23256	69991;69992;69993	chr2:178542893;178542892;178542891	chr2:179407620;179407619;179407618
Novex-1	23381	70366;70367;70368	chr2:178542893;178542892;178542891	chr2:179407620;179407619;179407618
Novex-2	23448	70567;70568;70569	chr2:178542893;178542892;178542891	chr2:179407620;179407619;179407618
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-154
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.2716
• 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
G/D	rs1421966339	-0.946	1.0	D	0.879	0.736	0.607940206691	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
G/D	rs1421966339	-0.946	1.0	D	0.879	0.736	0.607940206691	gnomAD-4.0.0	1.59212E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43336E-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
G/A	0.6094	likely_pathogenic	0.5693	pathogenic	-0.626	Destabilizing	1.0	D	0.779	deleterious	D	0.590394257	None	None	N
G/C	0.6857	likely_pathogenic	0.6497	pathogenic	-0.951	Destabilizing	1.0	D	0.866	deleterious	D	0.616537782	None	None	N
G/D	0.6807	likely_pathogenic	0.6627	pathogenic	-1.239	Destabilizing	1.0	D	0.879	deleterious	D	0.582047048	None	None	N
G/E	0.7544	likely_pathogenic	0.7235	pathogenic	-1.386	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
G/F	0.9432	likely_pathogenic	0.9314	pathogenic	-1.28	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
G/H	0.7864	likely_pathogenic	0.7678	pathogenic	-1.001	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
G/I	0.9593	likely_pathogenic	0.9433	pathogenic	-0.611	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
G/K	0.8154	likely_pathogenic	0.7904	pathogenic	-1.237	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
G/L	0.8885	likely_pathogenic	0.8662	pathogenic	-0.611	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
G/M	0.9173	likely_pathogenic	0.9008	pathogenic	-0.42	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
G/N	0.5935	likely_pathogenic	0.6022	pathogenic	-0.852	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
G/P	0.9948	likely_pathogenic	0.992	pathogenic	-0.58	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
G/Q	0.7079	likely_pathogenic	0.6805	pathogenic	-1.179	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
G/R	0.7024	likely_pathogenic	0.6483	pathogenic	-0.708	Destabilizing	1.0	D	0.898	deleterious	D	0.590596061	None	None	N
G/S	0.3253	likely_benign	0.3094	benign	-0.975	Destabilizing	1.0	D	0.859	deleterious	D	0.583459678	None	None	N
G/T	0.7503	likely_pathogenic	0.7088	pathogenic	-1.063	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
G/V	0.9128	likely_pathogenic	0.879	pathogenic	-0.58	Destabilizing	1.0	D	0.855	deleterious	D	0.616335977	None	None	N
G/W	0.8913	likely_pathogenic	0.8553	pathogenic	-1.468	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
G/Y	0.8892	likely_pathogenic	0.8683	pathogenic	-1.132	Destabilizing	1.0	D	0.869	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.