TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21652	65179;65180;65181	chr2:178584687;178584686;178584685	chr2:179449414;179449413;179449412
N2AB	20011	60256;60257;60258	chr2:178584687;178584686;178584685	chr2:179449414;179449413;179449412
N2A	19084	57475;57476;57477	chr2:178584687;178584686;178584685	chr2:179449414;179449413;179449412
N2B	12587	37984;37985;37986	chr2:178584687;178584686;178584685	chr2:179449414;179449413;179449412
Novex-1	12712	38359;38360;38361	chr2:178584687;178584686;178584685	chr2:179449414;179449413;179449412
Novex-2	12779	38560;38561;38562	chr2:178584687;178584686;178584685	chr2:179449414;179449413;179449412
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-44
• Domain position: 94
• Structural Position: 128
• Q(SASA): 0.2469
• 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
V/A	rs1386324100	None	0.025	N	0.409	0.237	0.532359089423	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	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
V/A	0.1483	likely_benign	0.1669	benign	-0.988	Destabilizing	0.025	N	0.409	neutral	N	0.4776553	None	None	N
V/C	0.6479	likely_pathogenic	0.629	pathogenic	-0.712	Destabilizing	0.869	D	0.533	neutral	None	None	None	None	N
V/D	0.3848	ambiguous	0.456	ambiguous	-0.69	Destabilizing	0.303	N	0.729	deleterious	N	0.478415768	None	None	N
V/E	0.2476	likely_benign	0.2596	benign	-0.761	Destabilizing	0.366	N	0.621	neutral	None	None	None	None	N
V/F	0.1594	likely_benign	0.1736	benign	-0.917	Destabilizing	0.097	N	0.561	neutral	N	0.478162279	None	None	N
V/G	0.2845	likely_benign	0.3331	benign	-1.216	Destabilizing	0.303	N	0.696	prob.delet.	N	0.479176237	None	None	N
V/H	0.4094	ambiguous	0.4265	ambiguous	-0.688	Destabilizing	0.869	D	0.722	deleterious	None	None	None	None	N
V/I	0.0685	likely_benign	0.0678	benign	-0.506	Destabilizing	None	N	0.095	neutral	N	0.493406999	None	None	N
V/K	0.1805	likely_benign	0.1949	benign	-0.824	Destabilizing	0.366	N	0.625	neutral	None	None	None	None	N
V/L	0.1149	likely_benign	0.1134	benign	-0.506	Destabilizing	None	N	0.121	neutral	N	0.465792015	None	None	N
V/M	0.1119	likely_benign	0.1132	benign	-0.383	Destabilizing	0.125	N	0.517	neutral	None	None	None	None	N
V/N	0.254	likely_benign	0.2893	benign	-0.526	Destabilizing	0.637	D	0.736	deleterious	None	None	None	None	N
V/P	0.4682	ambiguous	0.5454	ambiguous	-0.63	Destabilizing	0.637	D	0.659	prob.neutral	None	None	None	None	N
V/Q	0.2213	likely_benign	0.2249	benign	-0.767	Destabilizing	0.637	D	0.665	prob.neutral	None	None	None	None	N
V/R	0.1592	likely_benign	0.1762	benign	-0.236	Destabilizing	0.366	N	0.74	deleterious	None	None	None	None	N
V/S	0.2153	likely_benign	0.2546	benign	-0.981	Destabilizing	0.141	N	0.572	neutral	None	None	None	None	N
V/T	0.1142	likely_benign	0.1237	benign	-0.947	Destabilizing	0.075	N	0.465	neutral	None	None	None	None	N
V/W	0.6861	likely_pathogenic	0.6959	pathogenic	-1.012	Destabilizing	0.869	D	0.751	deleterious	None	None	None	None	N
V/Y	0.4465	ambiguous	0.453	ambiguous	-0.737	Destabilizing	0.366	N	0.575	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.