TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16607	50044;50045;50046	chr2:178612902;178612901;178612900	chr2:179477629;179477628;179477627
N2AB	14966	45121;45122;45123	chr2:178612902;178612901;178612900	chr2:179477629;179477628;179477627
N2A	14039	42340;42341;42342	chr2:178612902;178612901;178612900	chr2:179477629;179477628;179477627
N2B	7542	22849;22850;22851	chr2:178612902;178612901;178612900	chr2:179477629;179477628;179477627
Novex-1	7667	23224;23225;23226	chr2:178612902;178612901;178612900	chr2:179477629;179477628;179477627
Novex-2	7734	23425;23426;23427	chr2:178612902;178612901;178612900	chr2:179477629;179477628;179477627
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: Fn3-8
• Domain position: 57
• Structural Position: 88
• Q(SASA): 0.2399
• 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	rs747514142	0.142	0.007	N	0.188	0.18	0.257786959452	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
T/I	rs747514142	0.142	0.007	N	0.188	0.18	0.257786959452	gnomAD-4.0.0	3.18758E-06	None	None	None	None	N	None	0	0	None	0	2.79158E-05	None	0	0	2.8619E-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	0.0789	likely_benign	0.074	benign	-0.787	Destabilizing	0.047	N	0.169	neutral	N	0.473534732	None	None	N
T/C	0.4944	ambiguous	0.4288	ambiguous	-0.532	Destabilizing	0.983	D	0.318	neutral	None	None	None	None	N
T/D	0.3302	likely_benign	0.3354	benign	-0.186	Destabilizing	0.418	N	0.346	neutral	None	None	None	None	N
T/E	0.2698	likely_benign	0.2916	benign	-0.126	Destabilizing	0.418	N	0.273	neutral	None	None	None	None	N
T/F	0.2831	likely_benign	0.2695	benign	-0.843	Destabilizing	0.716	D	0.397	neutral	None	None	None	None	N
T/G	0.18	likely_benign	0.1685	benign	-1.066	Destabilizing	0.002	N	0.24	neutral	None	None	None	None	N
T/H	0.3323	likely_benign	0.3255	benign	-1.103	Destabilizing	0.951	D	0.333	neutral	None	None	None	None	N
T/I	0.2404	likely_benign	0.2254	benign	-0.119	Destabilizing	0.007	N	0.188	neutral	N	0.488894068	None	None	N
T/K	0.2771	likely_benign	0.3164	benign	-0.55	Destabilizing	0.264	N	0.277	neutral	None	None	None	None	N
T/L	0.1154	likely_benign	0.1035	benign	-0.119	Destabilizing	0.001	N	0.132	neutral	None	None	None	None	N
T/M	0.1034	likely_benign	0.0928	benign	-0.207	Destabilizing	0.061	N	0.213	neutral	None	None	None	None	N
T/N	0.1251	likely_benign	0.1152	benign	-0.692	Destabilizing	0.213	N	0.289	neutral	N	0.490414086	None	None	N
T/P	0.3889	ambiguous	0.4612	ambiguous	-0.311	Destabilizing	0.794	D	0.379	neutral	D	0.527529159	None	None	N
T/Q	0.235	likely_benign	0.2436	benign	-0.673	Destabilizing	0.716	D	0.367	neutral	None	None	None	None	N
T/R	0.2665	likely_benign	0.3186	benign	-0.395	Destabilizing	0.716	D	0.379	neutral	None	None	None	None	N
T/S	0.0975	likely_benign	0.0897	benign	-0.971	Destabilizing	0.003	N	0.085	neutral	N	0.439428814	None	None	N
T/V	0.1438	likely_benign	0.1335	benign	-0.311	Destabilizing	0.129	N	0.239	neutral	None	None	None	None	N
T/W	0.714	likely_pathogenic	0.7421	pathogenic	-0.9	Destabilizing	0.983	D	0.365	neutral	None	None	None	None	N
T/Y	0.3598	ambiguous	0.3671	ambiguous	-0.599	Destabilizing	0.94	D	0.373	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.