TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30386	91381;91382;91383	chr2:178551744;178551743;178551742	chr2:179416471;179416470;179416469
N2AB	28745	86458;86459;86460	chr2:178551744;178551743;178551742	chr2:179416471;179416470;179416469
N2A	27818	83677;83678;83679	chr2:178551744;178551743;178551742	chr2:179416471;179416470;179416469
N2B	21321	64186;64187;64188	chr2:178551744;178551743;178551742	chr2:179416471;179416470;179416469
Novex-1	21446	64561;64562;64563	chr2:178551744;178551743;178551742	chr2:179416471;179416470;179416469
Novex-2	21513	64762;64763;64764	chr2:178551744;178551743;178551742	chr2:179416471;179416470;179416469
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: Fn3-109
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.1359
• 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/G	None	None	0.211	N	0.643	0.136	0.270447802918	gnomAD-4.0.0	1.59127E-06	None	None	None	None	N	None	0	0	None	0	2.77331E-05	None	0	0	0	0	0
A/T	None	None	0.027	N	0.583	0.076	0.29385284311	gnomAD-4.0.0	2.40066E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62502E-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	0.3136	likely_benign	0.3274	benign	-0.842	Destabilizing	0.555	D	0.668	neutral	None	None	None	None	N
A/D	0.8272	likely_pathogenic	0.859	pathogenic	-1.268	Destabilizing	0.484	N	0.781	deleterious	N	0.456046263	None	None	N
A/E	0.7121	likely_pathogenic	0.7639	pathogenic	-1.066	Destabilizing	0.262	N	0.729	prob.delet.	None	None	None	None	N
A/F	0.3833	ambiguous	0.4648	ambiguous	-0.48	Destabilizing	0.38	N	0.777	deleterious	None	None	None	None	N
A/G	0.2546	likely_benign	0.2985	benign	-1.183	Destabilizing	0.211	N	0.643	neutral	N	0.515651927	None	None	N
A/H	0.8212	likely_pathogenic	0.8641	pathogenic	-1.675	Destabilizing	0.935	D	0.817	deleterious	None	None	None	None	N
A/I	0.0944	likely_benign	0.1071	benign	0.646	Stabilizing	None	N	0.46	neutral	None	None	None	None	N
A/K	0.8818	likely_pathogenic	0.9192	pathogenic	-0.745	Destabilizing	0.262	N	0.731	prob.delet.	None	None	None	None	N
A/L	0.1394	likely_benign	0.1615	benign	0.646	Stabilizing	0.005	N	0.573	neutral	None	None	None	None	N
A/M	0.1703	likely_benign	0.21	benign	0.303	Stabilizing	0.38	N	0.79	deleterious	None	None	None	None	N
A/N	0.572	likely_pathogenic	0.6563	pathogenic	-1.001	Destabilizing	0.791	D	0.803	deleterious	None	None	None	None	N
A/P	0.7127	likely_pathogenic	0.7584	pathogenic	0.251	Stabilizing	0.741	D	0.775	deleterious	N	0.515825286	None	None	N
A/Q	0.7097	likely_pathogenic	0.7695	pathogenic	-0.747	Destabilizing	0.791	D	0.791	deleterious	None	None	None	None	N
A/R	0.8567	likely_pathogenic	0.896	pathogenic	-1.027	Destabilizing	0.555	D	0.796	deleterious	None	None	None	None	N
A/S	0.1413	likely_benign	0.1552	benign	-1.525	Destabilizing	0.117	N	0.605	neutral	N	0.469514206	None	None	N
A/T	0.1003	likely_benign	0.1103	benign	-1.159	Destabilizing	0.027	N	0.583	neutral	N	0.469687564	None	None	N
A/V	0.0552	likely_benign	0.0577	benign	0.251	Stabilizing	None	N	0.21	neutral	N	0.324380139	None	None	N
A/W	0.8908	likely_pathogenic	0.9237	pathogenic	-1.185	Destabilizing	0.935	D	0.803	deleterious	None	None	None	None	N
A/Y	0.6668	likely_pathogenic	0.7365	pathogenic	-0.543	Destabilizing	0.555	D	0.805	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.