TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19427	58504;58505;58506	chr2:178594114;178594113;178594112	chr2:179458841;179458840;179458839
N2AB	17786	53581;53582;53583	chr2:178594114;178594113;178594112	chr2:179458841;179458840;179458839
N2A	16859	50800;50801;50802	chr2:178594114;178594113;178594112	chr2:179458841;179458840;179458839
N2B	10362	31309;31310;31311	chr2:178594114;178594113;178594112	chr2:179458841;179458840;179458839
Novex-1	10487	31684;31685;31686	chr2:178594114;178594113;178594112	chr2:179458841;179458840;179458839
Novex-2	10554	31885;31886;31887	chr2:178594114;178594113;178594112	chr2:179458841;179458840;179458839
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-118
• Domain position: 37
• Structural Position: 58
• Q(SASA): 0.2273
• 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
V/M	None	None	0.627	N	0.515	0.122	0.378847511475	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
V/A	0.4782	ambiguous	0.4116	ambiguous	-1.568	Destabilizing	0.165	N	0.443	neutral	N	0.516802866	None	None	N
V/C	0.7717	likely_pathogenic	0.7328	pathogenic	-0.972	Destabilizing	0.981	D	0.529	neutral	None	None	None	None	N
V/D	0.8039	likely_pathogenic	0.7277	pathogenic	-1.576	Destabilizing	0.818	D	0.651	neutral	None	None	None	None	N
V/E	0.7378	likely_pathogenic	0.6678	pathogenic	-1.419	Destabilizing	0.773	D	0.555	neutral	N	0.500130643	None	None	N
V/F	0.2376	likely_benign	0.2164	benign	-0.963	Destabilizing	0.69	D	0.523	neutral	None	None	None	None	N
V/G	0.5944	likely_pathogenic	0.5034	ambiguous	-2.022	Highly Destabilizing	0.773	D	0.581	neutral	N	0.518070314	None	None	N
V/H	0.882	likely_pathogenic	0.8467	pathogenic	-1.582	Destabilizing	0.981	D	0.647	neutral	None	None	None	None	N
V/I	0.063	likely_benign	0.0671	benign	-0.347	Destabilizing	0.002	N	0.246	neutral	None	None	None	None	N
V/K	0.8349	likely_pathogenic	0.7781	pathogenic	-1.228	Destabilizing	0.818	D	0.536	neutral	None	None	None	None	N
V/L	0.1451	likely_benign	0.1494	benign	-0.347	Destabilizing	None	N	0.179	neutral	N	0.404356367	None	None	N
V/M	0.192	likely_benign	0.1767	benign	-0.323	Destabilizing	0.627	D	0.515	neutral	N	0.509510681	None	None	N
V/N	0.708	likely_pathogenic	0.6495	pathogenic	-1.364	Destabilizing	0.932	D	0.655	neutral	None	None	None	None	N
V/P	0.8448	likely_pathogenic	0.826	pathogenic	-0.723	Destabilizing	0.932	D	0.603	neutral	None	None	None	None	N
V/Q	0.789	likely_pathogenic	0.73	pathogenic	-1.285	Destabilizing	0.932	D	0.605	neutral	None	None	None	None	N
V/R	0.8091	likely_pathogenic	0.75	pathogenic	-1.016	Destabilizing	0.818	D	0.657	neutral	None	None	None	None	N
V/S	0.6521	likely_pathogenic	0.5747	pathogenic	-1.971	Destabilizing	0.818	D	0.527	neutral	None	None	None	None	N
V/T	0.4975	ambiguous	0.4302	ambiguous	-1.67	Destabilizing	0.388	N	0.448	neutral	None	None	None	None	N
V/W	0.9002	likely_pathogenic	0.8729	pathogenic	-1.336	Destabilizing	0.981	D	0.676	prob.neutral	None	None	None	None	N
V/Y	0.7234	likely_pathogenic	0.6822	pathogenic	-0.928	Destabilizing	0.818	D	0.565	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.