TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6440	19543;19544;19545	chr2:178728608;178728607;178728606	chr2:179593335;179593334;179593333
N2AB	6123	18592;18593;18594	chr2:178728608;178728607;178728606	chr2:179593335;179593334;179593333
N2A	5196	15811;15812;15813	chr2:178728608;178728607;178728606	chr2:179593335;179593334;179593333
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-48
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.0752
• 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
A/T	rs1484285596	None	0.885	N	0.632	0.128	0.181679512989	gnomAD-4.0.0	2.73792E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.5986E-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
A/C	0.814	likely_pathogenic	0.7509	pathogenic	-0.633	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
A/D	0.9922	likely_pathogenic	0.9815	pathogenic	-2.115	Highly Destabilizing	0.982	D	0.75	deleterious	N	0.478849252	None	None	N
A/E	0.9841	likely_pathogenic	0.9673	pathogenic	-1.814	Destabilizing	0.953	D	0.727	prob.delet.	None	None	None	None	N
A/F	0.9023	likely_pathogenic	0.8196	pathogenic	-0.235	Destabilizing	0.998	D	0.77	deleterious	None	None	None	None	N
A/G	0.4479	ambiguous	0.3637	ambiguous	-1.188	Destabilizing	0.76	D	0.651	neutral	N	0.496767017	None	None	N
A/H	0.9836	likely_pathogenic	0.9725	pathogenic	-1.992	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
A/I	0.7971	likely_pathogenic	0.6685	pathogenic	0.988	Stabilizing	0.993	D	0.754	deleterious	None	None	None	None	N
A/K	0.9949	likely_pathogenic	0.9897	pathogenic	-0.471	Destabilizing	0.953	D	0.726	prob.delet.	None	None	None	None	N
A/L	0.7153	likely_pathogenic	0.6145	pathogenic	0.988	Stabilizing	0.953	D	0.715	prob.delet.	None	None	None	None	N
A/M	0.8214	likely_pathogenic	0.7209	pathogenic	0.439	Stabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
A/N	0.975	likely_pathogenic	0.9561	pathogenic	-1.082	Destabilizing	0.986	D	0.752	deleterious	None	None	None	None	N
A/P	0.9871	likely_pathogenic	0.978	pathogenic	0.497	Stabilizing	0.991	D	0.747	deleterious	N	0.485343712	None	None	N
A/Q	0.9718	likely_pathogenic	0.9559	pathogenic	-0.655	Destabilizing	0.993	D	0.769	deleterious	None	None	None	None	N
A/R	0.984	likely_pathogenic	0.9731	pathogenic	-1.062	Destabilizing	0.986	D	0.765	deleterious	None	None	None	None	N
A/S	0.3286	likely_benign	0.2641	benign	-1.428	Destabilizing	0.079	N	0.463	neutral	N	0.410012037	None	None	N
A/T	0.5332	ambiguous	0.3591	ambiguous	-0.97	Destabilizing	0.885	D	0.632	neutral	N	0.493302638	None	None	N
A/V	0.5179	ambiguous	0.3536	ambiguous	0.497	Stabilizing	0.939	D	0.651	neutral	N	0.453601746	None	None	N
A/W	0.9926	likely_pathogenic	0.9864	pathogenic	-1.167	Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	N
A/Y	0.9654	likely_pathogenic	0.9359	pathogenic	-0.505	Destabilizing	0.998	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.