TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24273	73042;73043;73044	chr2:178573315;178573314;178573313	chr2:179438042;179438041;179438040
N2AB	22632	68119;68120;68121	chr2:178573315;178573314;178573313	chr2:179438042;179438041;179438040
N2A	21705	65338;65339;65340	chr2:178573315;178573314;178573313	chr2:179438042;179438041;179438040
N2B	15208	45847;45848;45849	chr2:178573315;178573314;178573313	chr2:179438042;179438041;179438040
Novex-1	15333	46222;46223;46224	chr2:178573315;178573314;178573313	chr2:179438042;179438041;179438040
Novex-2	15400	46423;46424;46425	chr2:178573315;178573314;178573313	chr2:179438042;179438041;179438040
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-64
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.1351
• 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
N/H	None	None	1.0	N	0.767	0.356	0.326074293725	gnomAD-4.0.0	1.70312E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.03115E-06	0	0
N/S	None	None	0.999	N	0.607	0.292	0.285698343383	gnomAD-4.0.0	6.33644E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.24262E-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
N/A	0.6771	likely_pathogenic	0.6473	pathogenic	-1.051	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
N/C	0.4125	ambiguous	0.3897	ambiguous	-0.13	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
N/D	0.6947	likely_pathogenic	0.6573	pathogenic	-0.82	Destabilizing	0.999	D	0.643	neutral	N	0.493298155	None	None	N
N/E	0.9401	likely_pathogenic	0.9283	pathogenic	-0.645	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
N/F	0.9298	likely_pathogenic	0.9204	pathogenic	-0.649	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
N/G	0.6161	likely_pathogenic	0.57	pathogenic	-1.452	Destabilizing	0.999	D	0.595	neutral	None	None	None	None	N
N/H	0.3152	likely_benign	0.3136	benign	-1.013	Destabilizing	1.0	D	0.767	deleterious	N	0.475638427	None	None	N
N/I	0.6585	likely_pathogenic	0.6472	pathogenic	0.004	Stabilizing	1.0	D	0.809	deleterious	N	0.503262108	None	None	N
N/K	0.9437	likely_pathogenic	0.9352	pathogenic	-0.181	Destabilizing	1.0	D	0.74	deleterious	N	0.497159269	None	None	N
N/L	0.6269	likely_pathogenic	0.6267	pathogenic	0.004	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
N/M	0.7551	likely_pathogenic	0.7458	pathogenic	0.377	Stabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
N/P	0.8922	likely_pathogenic	0.8959	pathogenic	-0.318	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
N/Q	0.8352	likely_pathogenic	0.8118	pathogenic	-0.782	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
N/R	0.9159	likely_pathogenic	0.9041	pathogenic	-0.334	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
N/S	0.1247	likely_benign	0.113	benign	-1.063	Destabilizing	0.999	D	0.607	neutral	N	0.510187392	None	None	N
N/T	0.2651	likely_benign	0.2634	benign	-0.672	Destabilizing	0.999	D	0.701	prob.neutral	N	0.520441672	None	None	N
N/V	0.5941	likely_pathogenic	0.5787	pathogenic	-0.318	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
N/W	0.9727	likely_pathogenic	0.9666	pathogenic	-0.391	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
N/Y	0.6764	likely_pathogenic	0.6623	pathogenic	-0.142	Destabilizing	1.0	D	0.801	deleterious	N	0.488084369	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.