TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24607	74044;74045;74046	chr2:178572313;178572312;178572311	chr2:179437040;179437039;179437038
N2AB	22966	69121;69122;69123	chr2:178572313;178572312;178572311	chr2:179437040;179437039;179437038
N2A	22039	66340;66341;66342	chr2:178572313;178572312;178572311	chr2:179437040;179437039;179437038
N2B	15542	46849;46850;46851	chr2:178572313;178572312;178572311	chr2:179437040;179437039;179437038
Novex-1	15667	47224;47225;47226	chr2:178572313;178572312;178572311	chr2:179437040;179437039;179437038
Novex-2	15734	47425;47426;47427	chr2:178572313;178572312;178572311	chr2:179437040;179437039;179437038
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-66
• Domain position: 89
• Structural Position: 123
• Q(SASA): 0.1382
• 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	rs1286853195	None	1.0	N	0.835	0.386	0.384752662912	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/I	rs1286853195	None	1.0	N	0.835	0.386	0.384752662912	gnomAD-4.0.0	2.02998E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.40993E-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
T/A	0.3587	ambiguous	0.2466	benign	-0.771	Destabilizing	0.986	D	0.752	deleterious	N	0.465640658	None	None	N
T/C	0.7834	likely_pathogenic	0.6719	pathogenic	-0.437	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
T/D	0.9533	likely_pathogenic	0.901	pathogenic	0.125	Stabilizing	0.999	D	0.823	deleterious	None	None	None	None	N
T/E	0.9334	likely_pathogenic	0.8674	pathogenic	0.228	Stabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
T/F	0.8114	likely_pathogenic	0.6398	pathogenic	-0.589	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
T/G	0.7302	likely_pathogenic	0.582	pathogenic	-1.113	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
T/H	0.9089	likely_pathogenic	0.8153	pathogenic	-1.165	Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
T/I	0.4435	ambiguous	0.2821	benign	0.08	Stabilizing	1.0	D	0.835	deleterious	N	0.504469355	None	None	N
T/K	0.929	likely_pathogenic	0.8389	pathogenic	-0.247	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
T/L	0.22	likely_benign	0.1581	benign	0.08	Stabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
T/M	0.1577	likely_benign	0.1162	benign	-0.009	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
T/N	0.6257	likely_pathogenic	0.4654	ambiguous	-0.494	Destabilizing	0.999	D	0.807	deleterious	N	0.496039497	None	None	N
T/P	0.8184	likely_pathogenic	0.6743	pathogenic	-0.171	Destabilizing	0.999	D	0.832	deleterious	N	0.500292899	None	None	N
T/Q	0.8821	likely_pathogenic	0.7849	pathogenic	-0.424	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
T/R	0.9285	likely_pathogenic	0.8287	pathogenic	-0.279	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
T/S	0.4024	ambiguous	0.2933	benign	-0.871	Destabilizing	0.986	D	0.746	deleterious	N	0.499159535	None	None	N
T/V	0.3426	ambiguous	0.2408	benign	-0.171	Destabilizing	0.999	D	0.79	deleterious	None	None	None	None	N
T/W	0.973	likely_pathogenic	0.9297	pathogenic	-0.587	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
T/Y	0.906	likely_pathogenic	0.7894	pathogenic	-0.269	Destabilizing	1.0	D	0.909	deleterious	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.