TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23021	69286;69287;69288	chr2:178577274;178577273;178577272	chr2:179442001;179442000;179441999
N2AB	21380	64363;64364;64365	chr2:178577274;178577273;178577272	chr2:179442001;179442000;179441999
N2A	20453	61582;61583;61584	chr2:178577274;178577273;178577272	chr2:179442001;179442000;179441999
N2B	13956	42091;42092;42093	chr2:178577274;178577273;178577272	chr2:179442001;179442000;179441999
Novex-1	14081	42466;42467;42468	chr2:178577274;178577273;178577272	chr2:179442001;179442000;179441999
Novex-2	14148	42667;42668;42669	chr2:178577274;178577273;178577272	chr2:179442001;179442000;179441999
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: 72
• Structural Position: 157
• Q(SASA): 0.2056
• 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	rs1559469943	None	0.989	N	0.849	0.384	0.524894780827	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
T/I	rs1559469943	None	0.989	N	0.849	0.384	0.524894780827	gnomAD-4.0.0	6.8443E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99633E-07	0	0
T/P	None	None	0.989	D	0.849	0.662	0.589546583947	gnomAD-4.0.0	1.59245E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85994E-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	0.1073	likely_benign	0.1023	benign	-0.933	Destabilizing	0.726	D	0.595	neutral	N	0.494126254	None	None	N
T/C	0.4155	ambiguous	0.3882	ambiguous	-0.835	Destabilizing	0.999	D	0.836	deleterious	None	None	None	None	N
T/D	0.7002	likely_pathogenic	0.6717	pathogenic	-0.917	Destabilizing	0.983	D	0.777	deleterious	None	None	None	None	N
T/E	0.3868	ambiguous	0.3584	ambiguous	-0.916	Destabilizing	0.983	D	0.766	deleterious	None	None	None	None	N
T/F	0.3206	likely_benign	0.2782	benign	-1.306	Destabilizing	0.992	D	0.88	deleterious	None	None	None	None	N
T/G	0.4216	ambiguous	0.413	ambiguous	-1.134	Destabilizing	0.895	D	0.719	prob.delet.	None	None	None	None	N
T/H	0.3166	likely_benign	0.2778	benign	-1.519	Destabilizing	0.998	D	0.87	deleterious	None	None	None	None	N
T/I	0.1783	likely_benign	0.1637	benign	-0.486	Destabilizing	0.989	D	0.849	deleterious	N	0.517532731	None	None	N
T/K	0.247	likely_benign	0.229	benign	-0.619	Destabilizing	0.968	D	0.771	deleterious	None	None	None	None	N
T/L	0.1231	likely_benign	0.1196	benign	-0.486	Destabilizing	0.944	D	0.689	prob.neutral	None	None	None	None	N
T/M	0.0952	likely_benign	0.0924	benign	-0.114	Destabilizing	0.999	D	0.84	deleterious	None	None	None	None	N
T/N	0.228	likely_benign	0.2233	benign	-0.697	Destabilizing	0.957	D	0.731	prob.delet.	N	0.495696417	None	None	N
T/P	0.8641	likely_pathogenic	0.8825	pathogenic	-0.607	Destabilizing	0.989	D	0.849	deleterious	D	0.541401581	None	None	N
T/Q	0.266	likely_benign	0.249	benign	-1.015	Destabilizing	0.983	D	0.848	deleterious	None	None	None	None	N
T/R	0.2153	likely_benign	0.1941	benign	-0.358	Destabilizing	0.983	D	0.838	deleterious	None	None	None	None	N
T/S	0.1483	likely_benign	0.1396	benign	-0.912	Destabilizing	0.146	N	0.39	neutral	N	0.486884552	None	None	N
T/V	0.1504	likely_benign	0.1381	benign	-0.607	Destabilizing	0.944	D	0.613	neutral	None	None	None	None	N
T/W	0.6914	likely_pathogenic	0.6585	pathogenic	-1.229	Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	N
T/Y	0.3761	ambiguous	0.3408	ambiguous	-0.924	Destabilizing	0.997	D	0.879	deleterious	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.