TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5778	17557;17558;17559	chr2:178731434;178731433;178731432	chr2:179596161;179596160;179596159
N2AB	5461	16606;16607;16608	chr2:178731434;178731433;178731432	chr2:179596161;179596160;179596159
N2A	4534	13825;13826;13827	chr2:178731434;178731433;178731432	chr2:179596161;179596160;179596159
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: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-41
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.1503
• 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
M/R	None	None	0.784	N	0.555	0.42	0.639888206178	gnomAD-4.0.0	1.59128E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-05	0
M/V	None	None	0.003	N	0.047	0.125	0.428747304603	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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
M/A	0.5958	likely_pathogenic	0.6108	pathogenic	-2.291	Highly Destabilizing	0.003	N	0.165	neutral	None	None	None	None	N
M/C	0.8064	likely_pathogenic	0.8084	pathogenic	-1.653	Destabilizing	0.981	D	0.522	neutral	None	None	None	None	N
M/D	0.9543	likely_pathogenic	0.9544	pathogenic	-1.123	Destabilizing	0.828	D	0.621	neutral	None	None	None	None	N
M/E	0.729	likely_pathogenic	0.7282	pathogenic	-0.991	Destabilizing	0.704	D	0.542	neutral	None	None	None	None	N
M/F	0.4456	ambiguous	0.4509	ambiguous	-0.913	Destabilizing	0.704	D	0.361	neutral	None	None	None	None	N
M/G	0.8129	likely_pathogenic	0.827	pathogenic	-2.708	Highly Destabilizing	0.329	N	0.491	neutral	None	None	None	None	N
M/H	0.7289	likely_pathogenic	0.7372	pathogenic	-1.836	Destabilizing	0.981	D	0.577	neutral	None	None	None	None	N
M/I	0.3581	ambiguous	0.3658	ambiguous	-1.14	Destabilizing	0.001	N	0.06	neutral	N	0.364667403	None	None	N
M/K	0.2888	likely_benign	0.3136	benign	-1.097	Destabilizing	0.642	D	0.469	neutral	N	0.49885097	None	None	N
M/L	0.176	likely_benign	0.1838	benign	-1.14	Destabilizing	0.001	N	0.044	neutral	N	0.428372164	None	None	N
M/N	0.7254	likely_pathogenic	0.7286	pathogenic	-1.163	Destabilizing	0.828	D	0.638	neutral	None	None	None	None	N
M/P	0.9495	likely_pathogenic	0.9522	pathogenic	-1.501	Destabilizing	0.828	D	0.607	neutral	None	None	None	None	N
M/Q	0.3946	ambiguous	0.4089	ambiguous	-1.061	Destabilizing	0.828	D	0.466	neutral	None	None	None	None	N
M/R	0.3231	likely_benign	0.3527	ambiguous	-0.806	Destabilizing	0.784	D	0.555	neutral	N	0.469664213	None	None	N
M/S	0.6554	likely_pathogenic	0.6696	pathogenic	-1.833	Destabilizing	0.329	N	0.399	neutral	None	None	None	None	N
M/T	0.386	ambiguous	0.3855	ambiguous	-1.576	Destabilizing	0.425	N	0.363	neutral	N	0.427316159	None	None	N
M/V	0.1398	likely_benign	0.1474	benign	-1.501	Destabilizing	0.003	N	0.047	neutral	N	0.427406585	None	None	N
M/W	0.7838	likely_pathogenic	0.7817	pathogenic	-0.961	Destabilizing	0.995	D	0.514	neutral	None	None	None	None	N
M/Y	0.7029	likely_pathogenic	0.6936	pathogenic	-1.025	Destabilizing	0.936	D	0.576	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.