TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34291	103096;103097;103098	chr2:178533744;178533743;178533742	chr2:179398471;179398470;179398469
N2AB	32650	98173;98174;98175	chr2:178533744;178533743;178533742	chr2:179398471;179398470;179398469
N2A	31723	95392;95393;95394	chr2:178533744;178533743;178533742	chr2:179398471;179398470;179398469
N2B	25226	75901;75902;75903	chr2:178533744;178533743;178533742	chr2:179398471;179398470;179398469
Novex-1	25351	76276;76277;76278	chr2:178533744;178533743;178533742	chr2:179398471;179398470;179398469
Novex-2	25418	76477;76478;76479	chr2:178533744;178533743;178533742	chr2:179398471;179398470;179398469
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Ig-161
• Domain position: 34
• Structural Position: 48
• Q(SASA): 0.0643
• 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
W/C	None	None	0.999	D	0.853	0.907	0.786693768516	gnomAD-4.0.0	1.59102E-06	None	None	None	None	N	None	0	0	None	0	2.77254E-05	None	0	0	0	0	0
W/G	rs1690204801	None	0.997	D	0.842	0.922	0.834446456457	gnomAD-4.0.0	3.18196E-06	None	None	None	None	N	None	0	0	None	0	5.54508E-05	None	0	0	0	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
W/A	0.9959	likely_pathogenic	0.9967	pathogenic	-2.112	Highly Destabilizing	0.953	D	0.849	deleterious	None	None	None	None	N
W/C	0.9968	likely_pathogenic	0.9979	pathogenic	-1.345	Destabilizing	0.999	D	0.853	deleterious	D	0.708405239	None	None	N
W/D	0.9998	likely_pathogenic	0.9998	pathogenic	-2.802	Highly Destabilizing	0.998	D	0.881	deleterious	None	None	None	None	N
W/E	0.9997	likely_pathogenic	0.9997	pathogenic	-2.658	Highly Destabilizing	0.998	D	0.871	deleterious	None	None	None	None	N
W/F	0.6467	likely_pathogenic	0.6415	pathogenic	-1.228	Destabilizing	0.986	D	0.767	deleterious	None	None	None	None	N
W/G	0.9917	likely_pathogenic	0.9929	pathogenic	-2.379	Highly Destabilizing	0.997	D	0.842	deleterious	D	0.708203435	None	None	N
W/H	0.9985	likely_pathogenic	0.9985	pathogenic	-1.945	Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	N
W/I	0.9751	likely_pathogenic	0.9778	pathogenic	-1.13	Destabilizing	0.973	D	0.853	deleterious	None	None	None	None	N
W/K	0.9998	likely_pathogenic	0.9998	pathogenic	-2.125	Highly Destabilizing	0.993	D	0.871	deleterious	None	None	None	None	N
W/L	0.9472	likely_pathogenic	0.9552	pathogenic	-1.13	Destabilizing	0.046	N	0.74	prob.delet.	D	0.682665323	None	None	N
W/M	0.9921	likely_pathogenic	0.9931	pathogenic	-0.891	Destabilizing	0.986	D	0.809	deleterious	None	None	None	None	N
W/N	0.9997	likely_pathogenic	0.9997	pathogenic	-2.92	Highly Destabilizing	0.998	D	0.883	deleterious	None	None	None	None	N
W/P	0.9989	likely_pathogenic	0.999	pathogenic	-1.484	Destabilizing	0.998	D	0.881	deleterious	None	None	None	None	N
W/Q	0.9998	likely_pathogenic	0.9998	pathogenic	-2.572	Highly Destabilizing	0.998	D	0.881	deleterious	None	None	None	None	N
W/R	0.9994	likely_pathogenic	0.9994	pathogenic	-2.341	Highly Destabilizing	0.991	D	0.872	deleterious	D	0.692153713	None	None	N
W/S	0.9969	likely_pathogenic	0.9975	pathogenic	-2.994	Highly Destabilizing	0.991	D	0.87	deleterious	D	0.708405239	None	None	N
W/T	0.9972	likely_pathogenic	0.9974	pathogenic	-2.765	Highly Destabilizing	0.993	D	0.836	deleterious	None	None	None	None	N
W/V	0.9783	likely_pathogenic	0.9826	pathogenic	-1.484	Destabilizing	0.973	D	0.846	deleterious	None	None	None	None	N
W/Y	0.944	likely_pathogenic	0.9405	pathogenic	-1.101	Destabilizing	0.993	D	0.757	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.