TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8693	26302;26303;26304	chr2:178715109;178715108;178715107	chr2:179579836;179579835;179579834
N2AB	8376	25351;25352;25353	chr2:178715109;178715108;178715107	chr2:179579836;179579835;179579834
N2A	7449	22570;22571;22572	chr2:178715109;178715108;178715107	chr2:179579836;179579835;179579834
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: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-72
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.5139
• 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
S/P	None	None	0.944	D	0.692	0.36	0.265929055128	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
S/A	0.0778	likely_benign	0.0727	benign	-0.326	Destabilizing	0.035	N	0.51	neutral	N	0.483855904	None	None	N
S/C	0.1784	likely_benign	0.1679	benign	-0.179	Destabilizing	0.995	D	0.665	neutral	N	0.5206243	None	None	N
S/D	0.545	ambiguous	0.5227	ambiguous	0.06	Stabilizing	0.76	D	0.606	neutral	None	None	None	None	N
S/E	0.5688	likely_pathogenic	0.5516	ambiguous	-0.034	Destabilizing	0.816	D	0.602	neutral	None	None	None	None	N
S/F	0.3025	likely_benign	0.2714	benign	-0.898	Destabilizing	0.061	N	0.483	neutral	D	0.522418476	None	None	N
S/G	0.1345	likely_benign	0.1236	benign	-0.446	Destabilizing	0.018	N	0.285	neutral	None	None	None	None	N
S/H	0.4239	ambiguous	0.4216	ambiguous	-1.041	Destabilizing	0.999	D	0.663	neutral	None	None	None	None	N
S/I	0.2626	likely_benign	0.2226	benign	-0.14	Destabilizing	0.977	D	0.735	prob.delet.	None	None	None	None	N
S/K	0.7071	likely_pathogenic	0.7	pathogenic	-0.453	Destabilizing	0.922	D	0.602	neutral	None	None	None	None	N
S/L	0.1242	likely_benign	0.1117	benign	-0.14	Destabilizing	0.856	D	0.666	neutral	None	None	None	None	N
S/M	0.2193	likely_benign	0.211	benign	0.167	Stabilizing	0.999	D	0.665	neutral	None	None	None	None	N
S/N	0.1931	likely_benign	0.1837	benign	-0.136	Destabilizing	0.271	N	0.623	neutral	None	None	None	None	N
S/P	0.5495	ambiguous	0.494	ambiguous	-0.173	Destabilizing	0.944	D	0.692	prob.neutral	D	0.526882933	None	None	N
S/Q	0.534	ambiguous	0.5285	ambiguous	-0.417	Destabilizing	0.988	D	0.647	neutral	None	None	None	None	N
S/R	0.6437	likely_pathogenic	0.626	pathogenic	-0.271	Destabilizing	0.988	D	0.692	prob.neutral	None	None	None	None	N
S/T	0.083	likely_benign	0.0823	benign	-0.23	Destabilizing	0.004	N	0.341	neutral	N	0.516319223	None	None	N
S/V	0.2186	likely_benign	0.1886	benign	-0.173	Destabilizing	0.689	D	0.715	prob.delet.	None	None	None	None	N
S/W	0.4117	ambiguous	0.3885	ambiguous	-0.903	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
S/Y	0.2408	likely_benign	0.227	benign	-0.62	Destabilizing	0.94	D	0.751	deleterious	D	0.532134037	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.