TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2418	7477;7478;7479	chr2:178773916;178773915;178773914	chr2:179638643;179638642;179638641
N2AB	2418	7477;7478;7479	chr2:178773916;178773915;178773914	chr2:179638643;179638642;179638641
N2A	2418	7477;7478;7479	chr2:178773916;178773915;178773914	chr2:179638643;179638642;179638641
N2B	2372	7339;7340;7341	chr2:178773916;178773915;178773914	chr2:179638643;179638642;179638641
Novex-1	2372	7339;7340;7341	chr2:178773916;178773915;178773914	chr2:179638643;179638642;179638641
Novex-2	2372	7339;7340;7341	chr2:178773916;178773915;178773914	chr2:179638643;179638642;179638641
Novex-3	2418	7477;7478;7479	chr2:178773916;178773915;178773914	chr2:179638643;179638642;179638641

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-13
• Domain position: 63
• Structural Position: 145
• Q(SASA): 0.2941
• 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	0.704	N	0.413	0.207	0.230578612272	gnomAD-4.0.0	1.59055E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8566E-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	0.1119	likely_benign	0.112	benign	-0.458	Destabilizing	0.704	D	0.413	neutral	N	0.505669359	None	None	N
T/C	0.4193	ambiguous	0.3995	ambiguous	-0.145	Destabilizing	0.999	D	0.392	neutral	None	None	None	None	N
T/D	0.3553	ambiguous	0.3519	ambiguous	-0.839	Destabilizing	0.884	D	0.379	neutral	None	None	None	None	N
T/E	0.2706	likely_benign	0.2694	benign	-0.877	Destabilizing	0.939	D	0.367	neutral	None	None	None	None	N
T/F	0.3779	ambiguous	0.3688	ambiguous	-0.766	Destabilizing	0.997	D	0.463	neutral	None	None	None	None	N
T/G	0.2037	likely_benign	0.2022	benign	-0.669	Destabilizing	0.863	D	0.43	neutral	None	None	None	None	N
T/H	0.285	likely_benign	0.2775	benign	-1.136	Destabilizing	0.991	D	0.461	neutral	None	None	None	None	N
T/I	0.313	likely_benign	0.3055	benign	0.003	Stabilizing	0.988	D	0.344	neutral	D	0.630535392	None	None	N
T/K	0.1627	likely_benign	0.1579	benign	-0.657	Destabilizing	0.939	D	0.357	neutral	None	None	None	None	N
T/L	0.1351	likely_benign	0.1314	benign	0.003	Stabilizing	0.969	D	0.355	neutral	None	None	None	None	N
T/M	0.1163	likely_benign	0.118	benign	0.526	Stabilizing	0.999	D	0.375	neutral	None	None	None	None	N
T/N	0.1176	likely_benign	0.1156	benign	-0.573	Destabilizing	0.061	N	0.216	neutral	N	0.509622063	None	None	N
T/P	0.4925	ambiguous	0.5075	ambiguous	-0.12	Destabilizing	0.988	D	0.344	neutral	D	0.630654115	None	None	N
T/Q	0.1784	likely_benign	0.1757	benign	-0.865	Destabilizing	0.991	D	0.353	neutral	None	None	None	None	N
T/R	0.1535	likely_benign	0.1517	benign	-0.332	Destabilizing	0.991	D	0.332	neutral	None	None	None	None	N
T/S	0.1074	likely_benign	0.1056	benign	-0.664	Destabilizing	0.159	N	0.211	neutral	N	0.50152078	None	None	N
T/V	0.2128	likely_benign	0.2045	benign	-0.12	Destabilizing	0.969	D	0.379	neutral	None	None	None	None	N
T/W	0.69	likely_pathogenic	0.682	pathogenic	-0.787	Destabilizing	0.999	D	0.567	neutral	None	None	None	None	N
T/Y	0.425	ambiguous	0.4157	ambiguous	-0.51	Destabilizing	0.997	D	0.466	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.