TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24233	72922;72923;72924	chr2:178573435;178573434;178573433	chr2:179438162;179438161;179438160
N2AB	22592	67999;68000;68001	chr2:178573435;178573434;178573433	chr2:179438162;179438161;179438160
N2A	21665	65218;65219;65220	chr2:178573435;178573434;178573433	chr2:179438162;179438161;179438160
N2B	15168	45727;45728;45729	chr2:178573435;178573434;178573433	chr2:179438162;179438161;179438160
Novex-1	15293	46102;46103;46104	chr2:178573435;178573434;178573433	chr2:179438162;179438161;179438160
Novex-2	15360	46303;46304;46305	chr2:178573435;178573434;178573433	chr2:179438162;179438161;179438160
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: Fn3-64
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.4967
• 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	None	N	0.063	0.183	0.0138822411134	gnomAD-4.0.0	7.31964E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.35916E-07	0	0
T/S	rs768359972	-0.393	None	N	0.055	0.162	0.0666544352282	gnomAD-2.1.1	1.14E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.39509E-04	None	0	0	0
T/S	rs768359972	-0.393	None	N	0.055	0.162	0.0666544352282	gnomAD-4.0.0	3.75315E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	3.87087E-05	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	0.0503	likely_benign	0.0499	benign	-0.579	Destabilizing	None	N	0.063	neutral	N	0.387762401	None	None	N
T/C	0.3493	ambiguous	0.3753	ambiguous	-0.348	Destabilizing	0.676	D	0.369	neutral	None	None	None	None	N
T/D	0.3858	ambiguous	0.3869	ambiguous	0.14	Stabilizing	None	N	0.143	neutral	None	None	None	None	N
T/E	0.3591	ambiguous	0.3675	ambiguous	0.099	Stabilizing	0.016	N	0.306	neutral	None	None	None	None	N
T/F	0.3078	likely_benign	0.2872	benign	-0.844	Destabilizing	0.356	N	0.416	neutral	None	None	None	None	N
T/G	0.1635	likely_benign	0.1647	benign	-0.779	Destabilizing	0.016	N	0.337	neutral	None	None	None	None	N
T/H	0.3259	likely_benign	0.3208	benign	-1.065	Destabilizing	0.356	N	0.401	neutral	None	None	None	None	N
T/I	0.2209	likely_benign	0.1954	benign	-0.158	Destabilizing	0.055	N	0.404	neutral	N	0.50718716	None	None	N
T/K	0.3646	ambiguous	0.3558	ambiguous	-0.502	Destabilizing	0.038	N	0.336	neutral	None	None	None	None	N
T/L	0.106	likely_benign	0.0986	benign	-0.158	Destabilizing	0.038	N	0.304	neutral	None	None	None	None	N
T/M	0.0923	likely_benign	0.0844	benign	0.081	Stabilizing	0.356	N	0.368	neutral	None	None	None	None	N
T/N	0.1048	likely_benign	0.1019	benign	-0.344	Destabilizing	None	N	0.197	neutral	N	0.369907359	None	None	N
T/P	0.5257	ambiguous	0.4912	ambiguous	-0.267	Destabilizing	0.055	N	0.407	neutral	N	0.516748005	None	None	N
T/Q	0.2875	likely_benign	0.2833	benign	-0.553	Destabilizing	0.214	N	0.405	neutral	None	None	None	None	N
T/R	0.3345	likely_benign	0.3178	benign	-0.244	Destabilizing	0.072	N	0.405	neutral	None	None	None	None	N
T/S	0.0857	likely_benign	0.0861	benign	-0.621	Destabilizing	None	N	0.055	neutral	N	0.385703531	None	None	N
T/V	0.1348	likely_benign	0.1219	benign	-0.267	Destabilizing	0.038	N	0.22	neutral	None	None	None	None	N
T/W	0.7266	likely_pathogenic	0.7154	pathogenic	-0.786	Destabilizing	0.864	D	0.447	neutral	None	None	None	None	N
T/Y	0.3414	ambiguous	0.3247	benign	-0.536	Destabilizing	0.356	N	0.412	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.