TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26935	81028;81029;81030	chr2:178565329;178565328;178565327	chr2:179430056;179430055;179430054
N2AB	25294	76105;76106;76107	chr2:178565329;178565328;178565327	chr2:179430056;179430055;179430054
N2A	24367	73324;73325;73326	chr2:178565329;178565328;178565327	chr2:179430056;179430055;179430054
N2B	17870	53833;53834;53835	chr2:178565329;178565328;178565327	chr2:179430056;179430055;179430054
Novex-1	17995	54208;54209;54210	chr2:178565329;178565328;178565327	chr2:179430056;179430055;179430054
Novex-2	18062	54409;54410;54411	chr2:178565329;178565328;178565327	chr2:179430056;179430055;179430054
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-139
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.1417
• 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/A	None	None	0.016	N	0.487	0.085	0.0806252709748	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
T/A	0.0956	likely_benign	0.0894	benign	-1.091	Destabilizing	0.016	N	0.487	neutral	N	0.490723692	None	None	N
T/C	0.4259	ambiguous	0.3766	ambiguous	-1.045	Destabilizing	0.994	D	0.806	deleterious	None	None	None	None	N
T/D	0.9254	likely_pathogenic	0.9132	pathogenic	-2.241	Highly Destabilizing	0.959	D	0.759	deleterious	None	None	None	None	N
T/E	0.9146	likely_pathogenic	0.9052	pathogenic	-1.938	Destabilizing	0.959	D	0.751	deleterious	None	None	None	None	N
T/F	0.5834	likely_pathogenic	0.5711	pathogenic	-0.678	Destabilizing	0.979	D	0.843	deleterious	None	None	None	None	N
T/G	0.5283	ambiguous	0.4883	ambiguous	-1.571	Destabilizing	0.769	D	0.709	prob.delet.	None	None	None	None	N
T/H	0.7515	likely_pathogenic	0.7283	pathogenic	-1.729	Destabilizing	0.998	D	0.84	deleterious	None	None	None	None	N
T/I	0.316	likely_benign	0.2998	benign	0.207	Stabilizing	0.946	D	0.758	deleterious	N	0.509445526	None	None	N
T/K	0.8498	likely_pathogenic	0.8547	pathogenic	-0.428	Destabilizing	0.959	D	0.748	deleterious	None	None	None	None	N
T/L	0.1675	likely_benign	0.1582	benign	0.207	Stabilizing	0.769	D	0.666	neutral	None	None	None	None	N
T/M	0.1475	likely_benign	0.1316	benign	-0.107	Destabilizing	0.994	D	0.808	deleterious	None	None	None	None	N
T/N	0.5518	ambiguous	0.5148	ambiguous	-1.595	Destabilizing	0.973	D	0.741	deleterious	N	0.460402602	None	None	N
T/P	0.8588	likely_pathogenic	0.8535	pathogenic	-0.196	Destabilizing	0.946	D	0.801	deleterious	N	0.464263716	None	None	N
T/Q	0.7974	likely_pathogenic	0.7869	pathogenic	-1.077	Destabilizing	0.979	D	0.821	deleterious	None	None	None	None	N
T/R	0.7806	likely_pathogenic	0.7881	pathogenic	-0.984	Destabilizing	0.959	D	0.805	deleterious	None	None	None	None	N
T/S	0.191	likely_benign	0.1681	benign	-1.709	Destabilizing	0.716	D	0.61	neutral	N	0.433099541	None	None	N
T/V	0.1684	likely_benign	0.1627	benign	-0.196	Destabilizing	0.769	D	0.605	neutral	None	None	None	None	N
T/W	0.9218	likely_pathogenic	0.9086	pathogenic	-1.06	Destabilizing	0.998	D	0.832	deleterious	None	None	None	None	N
T/Y	0.7425	likely_pathogenic	0.7262	pathogenic	-0.573	Destabilizing	0.993	D	0.843	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.