TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14854	44785;44786;44787	chr2:178624720;178624719;178624718	chr2:179489447;179489446;179489445
N2AB	13213	39862;39863;39864	chr2:178624720;178624719;178624718	chr2:179489447;179489446;179489445
N2A	12286	37081;37082;37083	chr2:178624720;178624719;178624718	chr2:179489447;179489446;179489445
N2B	5789	17590;17591;17592	chr2:178624720;178624719;178624718	chr2:179489447;179489446;179489445
Novex-1	5914	17965;17966;17967	chr2:178624720;178624719;178624718	chr2:179489447;179489446;179489445
Novex-2	5981	18166;18167;18168	chr2:178624720;178624719;178624718	chr2:179489447;179489446;179489445
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-100
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.5001
• 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
E/K	None	None	0.958	N	0.521	0.345	0.462721901306	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
E/A	0.3147	likely_benign	0.3404	ambiguous	-0.254	Destabilizing	0.958	D	0.613	neutral	D	0.551559767	None	None	N
E/C	0.9419	likely_pathogenic	0.9514	pathogenic	-0.296	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/D	0.5343	ambiguous	0.5508	ambiguous	-0.524	Destabilizing	0.067	N	0.187	neutral	N	0.512114899	None	None	N
E/F	0.9035	likely_pathogenic	0.9044	pathogenic	0.31	Stabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
E/G	0.5325	ambiguous	0.5396	ambiguous	-0.519	Destabilizing	0.988	D	0.663	neutral	D	0.649764224	None	None	N
E/H	0.7939	likely_pathogenic	0.8153	pathogenic	0.714	Stabilizing	1.0	D	0.668	neutral	None	None	None	None	N
E/I	0.5885	likely_pathogenic	0.6332	pathogenic	0.436	Stabilizing	0.995	D	0.752	deleterious	None	None	None	None	N
E/K	0.4519	ambiguous	0.522	ambiguous	0.408	Stabilizing	0.958	D	0.521	neutral	N	0.504486228	None	None	N
E/L	0.6998	likely_pathogenic	0.7267	pathogenic	0.436	Stabilizing	0.995	D	0.726	prob.delet.	None	None	None	None	N
E/M	0.6957	likely_pathogenic	0.7155	pathogenic	0.305	Stabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
E/N	0.7049	likely_pathogenic	0.7293	pathogenic	-0.37	Destabilizing	0.982	D	0.687	prob.neutral	None	None	None	None	N
E/P	0.9401	likely_pathogenic	0.9485	pathogenic	0.227	Stabilizing	0.995	D	0.734	prob.delet.	None	None	None	None	N
E/Q	0.2903	likely_benign	0.3263	benign	-0.238	Destabilizing	0.994	D	0.629	neutral	N	0.503821375	None	None	N
E/R	0.5801	likely_pathogenic	0.6311	pathogenic	0.791	Stabilizing	0.995	D	0.699	prob.neutral	None	None	None	None	N
E/S	0.4833	ambiguous	0.5142	ambiguous	-0.483	Destabilizing	0.968	D	0.567	neutral	None	None	None	None	N
E/T	0.4282	ambiguous	0.489	ambiguous	-0.234	Destabilizing	0.991	D	0.72	prob.delet.	None	None	None	None	N
E/V	0.3817	ambiguous	0.4122	ambiguous	0.227	Stabilizing	0.994	D	0.709	prob.delet.	N	0.510286327	None	None	N
E/W	0.9792	likely_pathogenic	0.9803	pathogenic	0.572	Stabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
E/Y	0.8576	likely_pathogenic	0.8712	pathogenic	0.603	Stabilizing	1.0	D	0.725	prob.delet.	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.