TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18075	54448;54449;54450	chr2:178604866;178604865;178604864	chr2:179469593;179469592;179469591
N2AB	16434	49525;49526;49527	chr2:178604866;178604865;178604864	chr2:179469593;179469592;179469591
N2A	15507	46744;46745;46746	chr2:178604866;178604865;178604864	chr2:179469593;179469592;179469591
N2B	9010	27253;27254;27255	chr2:178604866;178604865;178604864	chr2:179469593;179469592;179469591
Novex-1	9135	27628;27629;27630	chr2:178604866;178604865;178604864	chr2:179469593;179469592;179469591
Novex-2	9202	27829;27830;27831	chr2:178604866;178604865;178604864	chr2:179469593;179469592;179469591
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: Fn3-19
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.3674
• 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/S	rs2054404821	None	0.001	N	0.085	0.106	0.128392430309	gnomAD-4.0.0	2.05463E-06	None	None	None	None	N	None	0	6.72797E-05	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
T/A	0.0947	likely_benign	0.1068	benign	-0.899	Destabilizing	0.041	N	0.188	neutral	N	0.492681854	None	None	N
T/C	0.3892	ambiguous	0.438	ambiguous	-0.488	Destabilizing	0.818	D	0.414	neutral	None	None	None	None	N
T/D	0.508	ambiguous	0.5778	pathogenic	-0.067	Destabilizing	0.388	N	0.353	neutral	None	None	None	None	N
T/E	0.4149	ambiguous	0.4919	ambiguous	-0.049	Destabilizing	0.388	N	0.352	neutral	None	None	None	None	N
T/F	0.3154	likely_benign	0.3672	ambiguous	-0.88	Destabilizing	0.69	D	0.455	neutral	None	None	None	None	N
T/G	0.2296	likely_benign	0.2558	benign	-1.178	Destabilizing	0.116	N	0.351	neutral	None	None	None	None	N
T/H	0.3321	likely_benign	0.375	ambiguous	-1.365	Destabilizing	0.932	D	0.42	neutral	None	None	None	None	N
T/I	0.2702	likely_benign	0.3356	benign	-0.241	Destabilizing	0.076	N	0.351	neutral	N	0.456241051	None	None	N
T/K	0.298	likely_benign	0.3492	ambiguous	-0.706	Destabilizing	0.388	N	0.348	neutral	None	None	None	None	N
T/L	0.1401	likely_benign	0.1546	benign	-0.241	Destabilizing	0.116	N	0.372	neutral	None	None	None	None	N
T/M	0.1012	likely_benign	0.1106	benign	0.005	Stabilizing	0.69	D	0.419	neutral	None	None	None	None	N
T/N	0.1637	likely_benign	0.1768	benign	-0.67	Destabilizing	0.324	N	0.258	neutral	N	0.506765872	None	None	N
T/P	0.7318	likely_pathogenic	0.7453	pathogenic	-0.428	Destabilizing	0.492	N	0.404	neutral	N	0.512134406	None	None	N
T/Q	0.2848	likely_benign	0.3216	benign	-0.786	Destabilizing	0.818	D	0.445	neutral	None	None	None	None	N
T/R	0.2595	likely_benign	0.3034	benign	-0.502	Destabilizing	0.69	D	0.433	neutral	None	None	None	None	N
T/S	0.0982	likely_benign	0.1064	benign	-0.999	Destabilizing	0.001	N	0.085	neutral	N	0.387839759	None	None	N
T/V	0.1817	likely_benign	0.2143	benign	-0.428	Destabilizing	0.001	N	0.095	neutral	None	None	None	None	N
T/W	0.6674	likely_pathogenic	0.7111	pathogenic	-0.802	Destabilizing	0.981	D	0.459	neutral	None	None	None	None	N
T/Y	0.3848	ambiguous	0.4215	ambiguous	-0.579	Destabilizing	0.818	D	0.455	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.