TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32414	97465;97466;97467	chr2:178542516;178542515;178542514	chr2:179407243;179407242;179407241
N2AB	30773	92542;92543;92544	chr2:178542516;178542515;178542514	chr2:179407243;179407242;179407241
N2A	29846	89761;89762;89763	chr2:178542516;178542515;178542514	chr2:179407243;179407242;179407241
N2B	23349	70270;70271;70272	chr2:178542516;178542515;178542514	chr2:179407243;179407242;179407241
Novex-1	23474	70645;70646;70647	chr2:178542516;178542515;178542514	chr2:179407243;179407242;179407241
Novex-2	23541	70846;70847;70848	chr2:178542516;178542515;178542514	chr2:179407243;179407242;179407241
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-124
• Domain position: 16
• Structural Position: 17
• Q(SASA): 0.4461
• 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	None	None	0.379	N	0.293	0.183	0.316198179892	gnomAD-4.0.0	1.5979E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43435E-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
A/C	0.4784	ambiguous	0.3792	ambiguous	-1.073	Destabilizing	0.992	D	0.311	neutral	None	None	None	None	N
A/D	0.3803	ambiguous	0.3539	ambiguous	-1.483	Destabilizing	0.004	N	0.333	neutral	N	0.502530701	None	None	N
A/E	0.3311	likely_benign	0.3112	benign	-1.597	Destabilizing	0.447	N	0.387	neutral	None	None	None	None	N
A/F	0.5793	likely_pathogenic	0.4475	ambiguous	-1.296	Destabilizing	0.92	D	0.479	neutral	None	None	None	None	N
A/G	0.1342	likely_benign	0.113	benign	-0.668	Destabilizing	0.002	N	0.093	neutral	N	0.484830375	None	None	N
A/H	0.5887	likely_pathogenic	0.5141	ambiguous	-0.63	Destabilizing	0.977	D	0.449	neutral	None	None	None	None	N
A/I	0.3942	ambiguous	0.3037	benign	-0.536	Destabilizing	0.92	D	0.397	neutral	None	None	None	None	N
A/K	0.5767	likely_pathogenic	0.5336	ambiguous	-0.741	Destabilizing	0.447	N	0.402	neutral	None	None	None	None	N
A/L	0.3364	likely_benign	0.2574	benign	-0.536	Destabilizing	0.617	D	0.393	neutral	None	None	None	None	N
A/M	0.3526	ambiguous	0.2701	benign	-0.386	Destabilizing	0.992	D	0.358	neutral	None	None	None	None	N
A/N	0.3	likely_benign	0.251	benign	-0.642	Destabilizing	0.447	N	0.475	neutral	None	None	None	None	N
A/P	0.296	likely_benign	0.2544	benign	-0.521	Destabilizing	0.896	D	0.392	neutral	N	0.499490396	None	None	N
A/Q	0.4404	ambiguous	0.3854	ambiguous	-1.014	Destabilizing	0.85	D	0.396	neutral	None	None	None	None	N
A/R	0.5591	ambiguous	0.4966	ambiguous	-0.271	Destabilizing	0.85	D	0.4	neutral	None	None	None	None	N
A/S	0.0889	likely_benign	0.0818	benign	-0.811	Destabilizing	0.007	N	0.087	neutral	N	0.461508011	None	None	N
A/T	0.1147	likely_benign	0.0994	benign	-0.864	Destabilizing	0.379	N	0.293	neutral	N	0.520673745	None	None	N
A/V	0.2101	likely_benign	0.1617	benign	-0.521	Destabilizing	0.549	D	0.331	neutral	N	0.488716252	None	None	N
A/W	0.8765	likely_pathogenic	0.8035	pathogenic	-1.43	Destabilizing	0.992	D	0.611	neutral	None	None	None	None	N
A/Y	0.6275	likely_pathogenic	0.5197	ambiguous	-1.028	Destabilizing	0.972	D	0.475	neutral	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.