TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22997	69214;69215;69216	chr2:178577346;178577345;178577344	chr2:179442073;179442072;179442071
N2AB	21356	64291;64292;64293	chr2:178577346;178577345;178577344	chr2:179442073;179442072;179442071
N2A	20429	61510;61511;61512	chr2:178577346;178577345;178577344	chr2:179442073;179442072;179442071
N2B	13932	42019;42020;42021	chr2:178577346;178577345;178577344	chr2:179442073;179442072;179442071
Novex-1	14057	42394;42395;42396	chr2:178577346;178577345;178577344	chr2:179442073;179442072;179442071
Novex-2	14124	42595;42596;42597	chr2:178577346;178577345;178577344	chr2:179442073;179442072;179442071
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-128
• Domain position: 48
• Structural Position: 125
• Q(SASA): 0.5179
• 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	0.051	0.084	0.130388298395	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
T/N	rs886043272	None	0.029	N	0.236	0.112	0.351614576976	gnomAD-4.0.0	1.36872E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.31922E-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	0.0773	likely_benign	0.0781	benign	-0.435	Destabilizing	None	N	0.051	neutral	N	0.490154129	None	None	N
T/C	0.3328	likely_benign	0.2982	benign	-0.141	Destabilizing	0.676	D	0.387	neutral	None	None	None	None	N
T/D	0.2548	likely_benign	0.2454	benign	0.081	Stabilizing	None	N	0.135	neutral	None	None	None	None	N
T/E	0.1987	likely_benign	0.1886	benign	-0.003	Destabilizing	None	N	0.109	neutral	None	None	None	None	N
T/F	0.1956	likely_benign	0.1616	benign	-0.981	Destabilizing	0.356	N	0.435	neutral	None	None	None	None	N
T/G	0.2203	likely_benign	0.2119	benign	-0.555	Destabilizing	0.016	N	0.314	neutral	None	None	None	None	N
T/H	0.1813	likely_benign	0.1614	benign	-0.936	Destabilizing	0.356	N	0.419	neutral	None	None	None	None	N
T/I	0.1044	likely_benign	0.09	benign	-0.237	Destabilizing	0.171	N	0.417	neutral	N	0.47609154	None	None	N
T/K	0.1622	likely_benign	0.146	benign	-0.294	Destabilizing	0.038	N	0.331	neutral	None	None	None	None	N
T/L	0.0912	likely_benign	0.0819	benign	-0.237	Destabilizing	0.038	N	0.331	neutral	None	None	None	None	N
T/M	0.0887	likely_benign	0.0848	benign	0.131	Stabilizing	0.628	D	0.389	neutral	None	None	None	None	N
T/N	0.0967	likely_benign	0.093	benign	-0.041	Destabilizing	0.029	N	0.236	neutral	N	0.495061303	None	None	N
T/P	0.4018	ambiguous	0.4247	ambiguous	-0.275	Destabilizing	0.055	N	0.389	neutral	N	0.512281627	None	None	N
T/Q	0.1688	likely_benign	0.1616	benign	-0.331	Destabilizing	0.038	N	0.387	neutral	None	None	None	None	N
T/R	0.1548	likely_benign	0.1388	benign	-0.014	Destabilizing	0.072	N	0.41	neutral	None	None	None	None	N
T/S	0.089	likely_benign	0.0852	benign	-0.256	Destabilizing	None	N	0.059	neutral	N	0.429028312	None	None	N
T/V	0.0991	likely_benign	0.0871	benign	-0.275	Destabilizing	0.038	N	0.237	neutral	None	None	None	None	N
T/W	0.5337	ambiguous	0.5001	ambiguous	-0.959	Destabilizing	0.864	D	0.451	neutral	None	None	None	None	N
T/Y	0.2142	likely_benign	0.194	benign	-0.677	Destabilizing	0.356	N	0.439	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.