TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13791	41596;41597;41598	chr2:178636200;178636199;178636198	chr2:179500927;179500926;179500925
N2AB	12150	36673;36674;36675	chr2:178636200;178636199;178636198	chr2:179500927;179500926;179500925
N2A	11223	33892;33893;33894	chr2:178636200;178636199;178636198	chr2:179500927;179500926;179500925
N2B	4726	14401;14402;14403	chr2:178636200;178636199;178636198	chr2:179500927;179500926;179500925
Novex-1	4851	14776;14777;14778	chr2:178636200;178636199;178636198	chr2:179500927;179500926;179500925
Novex-2	4918	14977;14978;14979	chr2:178636200;178636199;178636198	chr2:179500927;179500926;179500925
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-88
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.7328
• 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
T/I	rs2154230629	None	0.994	N	0.449	0.366	0.250039746154	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
T/I	rs2154230629	None	0.994	N	0.449	0.366	0.250039746154	gnomAD-4.0.0	6.57376E-06	None	None	None	None	N	None	0	6.54965E-05	None	0	0	None	0	0	0	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
T/A	0.242	likely_benign	0.2643	benign	-0.333	Destabilizing	0.835	D	0.454	neutral	N	0.332871317	None	None	N
T/C	0.806	likely_pathogenic	0.8347	pathogenic	-0.446	Destabilizing	1.0	D	0.504	neutral	None	None	None	None	N
T/D	0.8319	likely_pathogenic	0.8718	pathogenic	0.107	Stabilizing	0.97	D	0.474	neutral	None	None	None	None	N
T/E	0.6845	likely_pathogenic	0.752	pathogenic	0.106	Stabilizing	0.97	D	0.493	neutral	None	None	None	None	N
T/F	0.6726	likely_pathogenic	0.7383	pathogenic	-0.452	Destabilizing	0.999	D	0.673	prob.neutral	None	None	None	None	N
T/G	0.7526	likely_pathogenic	0.768	pathogenic	-0.568	Destabilizing	0.97	D	0.487	neutral	None	None	None	None	N
T/H	0.6778	likely_pathogenic	0.7422	pathogenic	-0.806	Destabilizing	1.0	D	0.651	prob.neutral	None	None	None	None	N
T/I	0.4616	ambiguous	0.5072	ambiguous	0.186	Stabilizing	0.994	D	0.449	neutral	N	0.325428053	None	None	N
T/K	0.6484	likely_pathogenic	0.7357	pathogenic	-0.544	Destabilizing	0.961	D	0.483	neutral	N	0.326108615	None	None	N
T/L	0.3043	likely_benign	0.3389	benign	0.186	Stabilizing	0.985	D	0.425	neutral	None	None	None	None	N
T/M	0.1783	likely_benign	0.2027	benign	0.043	Stabilizing	1.0	D	0.458	neutral	None	None	None	None	N
T/N	0.3942	ambiguous	0.4403	ambiguous	-0.522	Destabilizing	0.97	D	0.415	neutral	None	None	None	None	N
T/P	0.5769	likely_pathogenic	0.6024	pathogenic	0.046	Stabilizing	0.994	D	0.451	neutral	N	0.427184355	None	None	N
T/Q	0.5923	likely_pathogenic	0.6509	pathogenic	-0.589	Destabilizing	0.996	D	0.463	neutral	None	None	None	None	N
T/R	0.5858	likely_pathogenic	0.6818	pathogenic	-0.37	Destabilizing	0.994	D	0.469	neutral	N	0.335328715	None	None	N
T/S	0.2864	likely_benign	0.3146	benign	-0.73	Destabilizing	0.287	N	0.207	neutral	N	0.35319199	None	None	N
T/V	0.3273	likely_benign	0.345	ambiguous	0.046	Stabilizing	0.985	D	0.369	neutral	None	None	None	None	N
T/W	0.9012	likely_pathogenic	0.9276	pathogenic	-0.504	Destabilizing	1.0	D	0.732	deleterious	None	None	None	None	N
T/Y	0.7293	likely_pathogenic	0.7853	pathogenic	-0.217	Destabilizing	0.999	D	0.677	prob.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.