TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19215	57868;57869;57870	chr2:178595711;178595710;178595709	chr2:179460438;179460437;179460436
N2AB	17574	52945;52946;52947	chr2:178595711;178595710;178595709	chr2:179460438;179460437;179460436
N2A	16647	50164;50165;50166	chr2:178595711;178595710;178595709	chr2:179460438;179460437;179460436
N2B	10150	30673;30674;30675	chr2:178595711;178595710;178595709	chr2:179460438;179460437;179460436
Novex-1	10275	31048;31049;31050	chr2:178595711;178595710;178595709	chr2:179460438;179460437;179460436
Novex-2	10342	31249;31250;31251	chr2:178595711;178595710;178595709	chr2:179460438;179460437;179460436
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-27
• Domain position: 33
• Structural Position: 34
• Q(SASA): 0.64
• Predicted PPI site: I

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
P/S	rs776531074	0.017	0.193	N	0.393	0.245	0.208000267992	gnomAD-2.1.1	4.17E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	9.21E-06	0
P/S	rs776531074	0.017	0.193	N	0.393	0.245	0.208000267992	gnomAD-4.0.0	1.60373E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.87527E-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
P/A	0.0736	likely_benign	0.08	benign	-0.399	Destabilizing	None	N	0.135	neutral	N	0.46995971	None	None	I
P/C	0.5487	ambiguous	0.6387	pathogenic	-0.576	Destabilizing	0.944	D	0.499	neutral	None	None	None	None	I
P/D	0.5549	ambiguous	0.6439	pathogenic	-0.142	Destabilizing	0.818	D	0.444	neutral	None	None	None	None	I
P/E	0.3494	ambiguous	0.3932	ambiguous	-0.268	Destabilizing	0.388	N	0.425	neutral	None	None	None	None	I
P/F	0.5628	ambiguous	0.6859	pathogenic	-0.764	Destabilizing	0.527	D	0.522	neutral	None	None	None	None	I
P/G	0.3854	ambiguous	0.4435	ambiguous	-0.504	Destabilizing	0.241	N	0.47	neutral	None	None	None	None	I
P/H	0.2612	likely_benign	0.3074	benign	-0.153	Destabilizing	0.981	D	0.498	neutral	None	None	None	None	I
P/I	0.2886	likely_benign	0.3591	ambiguous	-0.28	Destabilizing	0.241	N	0.474	neutral	None	None	None	None	I
P/K	0.3793	ambiguous	0.4359	ambiguous	-0.213	Destabilizing	0.388	N	0.435	neutral	None	None	None	None	I
P/L	0.1343	likely_benign	0.1652	benign	-0.28	Destabilizing	0.001	N	0.262	neutral	N	0.498074776	None	None	I
P/M	0.2905	likely_benign	0.35	ambiguous	-0.222	Destabilizing	0.69	D	0.501	neutral	None	None	None	None	I
P/N	0.3547	ambiguous	0.4387	ambiguous	0.013	Stabilizing	0.818	D	0.529	neutral	None	None	None	None	I
P/Q	0.182	likely_benign	0.1968	benign	-0.256	Destabilizing	0.773	D	0.463	neutral	N	0.514211919	None	None	I
P/R	0.2573	likely_benign	0.2936	benign	0.271	Stabilizing	0.773	D	0.529	neutral	N	0.474601696	None	None	I
P/S	0.144	likely_benign	0.1694	benign	-0.353	Destabilizing	0.193	N	0.393	neutral	N	0.476296763	None	None	I
P/T	0.1145	likely_benign	0.1301	benign	-0.379	Destabilizing	0.324	N	0.398	neutral	N	0.471118976	None	None	I
P/V	0.1737	likely_benign	0.2132	benign	-0.286	Destabilizing	0.241	N	0.469	neutral	None	None	None	None	I
P/W	0.7713	likely_pathogenic	0.8483	pathogenic	-0.827	Destabilizing	0.981	D	0.619	neutral	None	None	None	None	I
P/Y	0.543	ambiguous	0.6588	pathogenic	-0.498	Destabilizing	0.818	D	0.511	neutral	None	None	None	None	I

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.