TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21461	64606;64607;64608	chr2:178586520;178586519;178586518	chr2:179451247;179451246;179451245
N2AB	19820	59683;59684;59685	chr2:178586520;178586519;178586518	chr2:179451247;179451246;179451245
N2A	18893	56902;56903;56904	chr2:178586520;178586519;178586518	chr2:179451247;179451246;179451245
N2B	12396	37411;37412;37413	chr2:178586520;178586519;178586518	chr2:179451247;179451246;179451245
Novex-1	12521	37786;37787;37788	chr2:178586520;178586519;178586518	chr2:179451247;179451246;179451245
Novex-2	12588	37987;37988;37989	chr2:178586520;178586519;178586518	chr2:179451247;179451246;179451245
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: Fn3-43
• Domain position: 96
• Structural Position: 130
• Q(SASA): 0.0853
• 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/V	None	None	0.003	N	0.096	0.16	0.275641507738	gnomAD-4.0.0	1.59305E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86193E-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	0.4846	ambiguous	0.4722	ambiguous	-1.88	Destabilizing	0.982	D	0.611	neutral	None	None	None	None	N
A/D	0.9889	likely_pathogenic	0.984	pathogenic	-3.136	Highly Destabilizing	0.976	D	0.693	prob.delet.	N	0.501907253	None	None	N
A/E	0.9666	likely_pathogenic	0.9588	pathogenic	-2.993	Highly Destabilizing	0.939	D	0.657	prob.neutral	None	None	None	None	N
A/F	0.862	likely_pathogenic	0.8567	pathogenic	-0.9	Destabilizing	0.897	D	0.693	prob.delet.	None	None	None	None	N
A/G	0.4956	ambiguous	0.446	ambiguous	-1.743	Destabilizing	0.92	D	0.605	neutral	N	0.501653763	None	None	N
A/H	0.987	likely_pathogenic	0.9848	pathogenic	-1.801	Destabilizing	0.995	D	0.633	neutral	None	None	None	None	N
A/I	0.2272	likely_benign	0.2089	benign	-0.376	Destabilizing	0.003	N	0.309	neutral	None	None	None	None	N
A/K	0.9888	likely_pathogenic	0.986	pathogenic	-1.51	Destabilizing	0.834	D	0.67	prob.neutral	None	None	None	None	N
A/L	0.3375	likely_benign	0.3335	benign	-0.376	Destabilizing	0.182	N	0.509	neutral	None	None	None	None	N
A/M	0.4541	ambiguous	0.4511	ambiguous	-0.817	Destabilizing	0.897	D	0.698	prob.delet.	None	None	None	None	N
A/N	0.9236	likely_pathogenic	0.9052	pathogenic	-1.864	Destabilizing	0.982	D	0.738	deleterious	None	None	None	None	N
A/P	0.6136	likely_pathogenic	0.5658	pathogenic	-0.669	Destabilizing	0.976	D	0.703	prob.delet.	D	0.523146408	None	None	N
A/Q	0.9482	likely_pathogenic	0.946	pathogenic	-1.803	Destabilizing	0.982	D	0.722	deleterious	None	None	None	None	N
A/R	0.9719	likely_pathogenic	0.967	pathogenic	-1.381	Destabilizing	0.982	D	0.701	prob.delet.	None	None	None	None	N
A/S	0.3531	ambiguous	0.326	benign	-2.156	Highly Destabilizing	0.791	D	0.587	neutral	N	0.499118868	None	None	N
A/T	0.3353	likely_benign	0.2857	benign	-1.915	Destabilizing	0.651	D	0.583	neutral	N	0.5219329	None	None	N
A/V	0.1392	likely_benign	0.1185	benign	-0.669	Destabilizing	0.003	N	0.096	neutral	N	0.428558592	None	None	N
A/W	0.9893	likely_pathogenic	0.9885	pathogenic	-1.527	Destabilizing	0.995	D	0.729	deleterious	None	None	None	None	N
A/Y	0.9648	likely_pathogenic	0.9573	pathogenic	-1.099	Destabilizing	0.982	D	0.722	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.