TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21478	64657;64658;64659	chr2:178585312;178585311;178585310	chr2:179450039;179450038;179450037
N2AB	19837	59734;59735;59736	chr2:178585312;178585311;178585310	chr2:179450039;179450038;179450037
N2A	18910	56953;56954;56955	chr2:178585312;178585311;178585310	chr2:179450039;179450038;179450037
N2B	12413	37462;37463;37464	chr2:178585312;178585311;178585310	chr2:179450039;179450038;179450037
Novex-1	12538	37837;37838;37839	chr2:178585312;178585311;178585310	chr2:179450039;179450038;179450037
Novex-2	12605	38038;38039;38040	chr2:178585312;178585311;178585310	chr2:179450039;179450038;179450037
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-124
• Domain position: 10
• Structural Position: 16
• Q(SASA): 0.1446
• 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
I/M	None	None	0.988	D	0.529	0.417	0.410868550352	gnomAD-4.0.0	1.59992E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88509E-05	0	0	0	0
I/V	None	None	0.061	N	0.137	0.154	0.404453528171	gnomAD-4.0.0	6.85842E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.20627E-06	1.16869E-05	1.66063E-05

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
I/A	0.4758	ambiguous	0.3082	benign	-2.156	Highly Destabilizing	0.079	N	0.272	neutral	None	None	None	None	N
I/C	0.7386	likely_pathogenic	0.6339	pathogenic	-1.28	Destabilizing	0.999	D	0.557	neutral	None	None	None	None	N
I/D	0.9557	likely_pathogenic	0.8974	pathogenic	-2.014	Highly Destabilizing	0.884	D	0.609	neutral	None	None	None	None	N
I/E	0.879	likely_pathogenic	0.7718	pathogenic	-1.889	Destabilizing	0.17	N	0.373	neutral	None	None	None	None	N
I/F	0.4924	ambiguous	0.3729	ambiguous	-1.311	Destabilizing	0.988	D	0.561	neutral	N	0.514975216	None	None	N
I/G	0.8585	likely_pathogenic	0.725	pathogenic	-2.614	Highly Destabilizing	0.884	D	0.581	neutral	None	None	None	None	N
I/H	0.8977	likely_pathogenic	0.8044	pathogenic	-1.969	Destabilizing	0.999	D	0.59	neutral	None	None	None	None	N
I/K	0.8422	likely_pathogenic	0.7122	pathogenic	-1.638	Destabilizing	0.939	D	0.606	neutral	None	None	None	None	N
I/L	0.2196	likely_benign	0.1629	benign	-0.892	Destabilizing	0.509	D	0.316	neutral	N	0.470144216	None	None	N
I/M	0.1742	likely_benign	0.1287	benign	-0.669	Destabilizing	0.988	D	0.529	neutral	D	0.533830335	None	None	N
I/N	0.7574	likely_pathogenic	0.5712	pathogenic	-1.667	Destabilizing	0.988	D	0.624	neutral	D	0.53435041	None	None	N
I/P	0.9784	likely_pathogenic	0.9647	pathogenic	-1.288	Destabilizing	0.991	D	0.633	neutral	None	None	None	None	N
I/Q	0.8095	likely_pathogenic	0.6684	pathogenic	-1.68	Destabilizing	0.982	D	0.631	neutral	None	None	None	None	N
I/R	0.7792	likely_pathogenic	0.6308	pathogenic	-1.184	Destabilizing	0.982	D	0.631	neutral	None	None	None	None	N
I/S	0.6301	likely_pathogenic	0.4377	ambiguous	-2.338	Highly Destabilizing	0.852	D	0.515	neutral	N	0.514975216	None	None	N
I/T	0.502	ambiguous	0.3209	benign	-2.086	Highly Destabilizing	0.92	D	0.493	neutral	N	0.487076538	None	None	N
I/V	0.0723	likely_benign	0.0597	benign	-1.288	Destabilizing	0.061	N	0.137	neutral	N	0.372380022	None	None	N
I/W	0.9571	likely_pathogenic	0.9374	pathogenic	-1.604	Destabilizing	0.999	D	0.582	neutral	None	None	None	None	N
I/Y	0.8532	likely_pathogenic	0.7714	pathogenic	-1.33	Destabilizing	0.997	D	0.611	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.