TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23960	72103;72104;72105	chr2:178574254;178574253;178574252	chr2:179438981;179438980;179438979
N2AB	22319	67180;67181;67182	chr2:178574254;178574253;178574252	chr2:179438981;179438980;179438979
N2A	21392	64399;64400;64401	chr2:178574254;178574253;178574252	chr2:179438981;179438980;179438979
N2B	14895	44908;44909;44910	chr2:178574254;178574253;178574252	chr2:179438981;179438980;179438979
Novex-1	15020	45283;45284;45285	chr2:178574254;178574253;178574252	chr2:179438981;179438980;179438979
Novex-2	15087	45484;45485;45486	chr2:178574254;178574253;178574252	chr2:179438981;179438980;179438979
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-62
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.1606
• 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
I/M	rs1366447660	-0.921	0.006	N	0.457	0.19	0.225902525712	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
I/M	rs1366447660	-0.921	0.006	N	0.457	0.19	0.225902525712	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	1.47E-05	0	0
I/M	rs1366447660	-0.921	0.006	N	0.457	0.19	0.225902525712	gnomAD-4.0.0	3.10035E-06	None	None	None	None	N	None	1.33554E-05	0	None	0	0	None	0	0	3.39227E-06	0	0
I/T	rs568223521	-2.237	None	N	0.369	0.119	0.612591404863	gnomAD-2.1.1	1.43E-05	None	None	None	None	N	None	1.65426E-04	0	None	0	0	None	0	None	0	0	0
I/T	rs568223521	-2.237	None	N	0.369	0.119	0.612591404863	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	9.65E-05	0	0	0	0	None	0	0	0	0	0
I/T	rs568223521	-2.237	None	N	0.369	0.119	0.612591404863	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
I/T	rs568223521	-2.237	None	N	0.369	0.119	0.612591404863	gnomAD-4.0.0	2.62771E-05	None	None	None	None	N	None	9.62186E-05	0	None	0	0	None	0	0	0	0	0
I/V	rs1198927435	None	None	N	0.231	0.052	0.27855597813	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/V	rs1198927435	None	None	N	0.231	0.052	0.27855597813	gnomAD-4.0.0	2.02992E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.4099E-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
I/A	0.192	likely_benign	0.2494	benign	-2.211	Highly Destabilizing	0.007	N	0.534	neutral	None	None	None	None	N
I/C	0.5789	likely_pathogenic	0.6634	pathogenic	-1.413	Destabilizing	0.356	N	0.649	neutral	None	None	None	None	N
I/D	0.6673	likely_pathogenic	0.7152	pathogenic	-2.12	Highly Destabilizing	0.072	N	0.627	neutral	None	None	None	None	N
I/E	0.6014	likely_pathogenic	0.6488	pathogenic	-2.027	Highly Destabilizing	0.016	N	0.597	neutral	None	None	None	None	N
I/F	0.1423	likely_benign	0.1518	benign	-1.415	Destabilizing	0.055	N	0.586	neutral	N	0.468797891	None	None	N
I/G	0.5799	likely_pathogenic	0.6754	pathogenic	-2.629	Highly Destabilizing	0.031	N	0.609	neutral	None	None	None	None	N
I/H	0.3898	ambiguous	0.4397	ambiguous	-1.84	Destabilizing	0.356	N	0.659	neutral	None	None	None	None	N
I/K	0.4866	ambiguous	0.545	ambiguous	-1.702	Destabilizing	0.016	N	0.602	neutral	None	None	None	None	N
I/L	0.0998	likely_benign	0.1168	benign	-1.071	Destabilizing	0.002	N	0.443	neutral	N	0.514342418	None	None	N
I/M	0.0725	likely_benign	0.087	benign	-0.838	Destabilizing	0.006	N	0.457	neutral	N	0.48749803	None	None	N
I/N	0.206	likely_benign	0.2172	benign	-1.72	Destabilizing	0.055	N	0.625	neutral	N	0.51668929	None	None	N
I/P	0.9641	likely_pathogenic	0.9711	pathogenic	-1.425	Destabilizing	0.136	N	0.617	neutral	None	None	None	None	N
I/Q	0.396	ambiguous	0.4625	ambiguous	-1.808	Destabilizing	0.003	N	0.541	neutral	None	None	None	None	N
I/R	0.3762	ambiguous	0.4198	ambiguous	-1.104	Destabilizing	0.072	N	0.617	neutral	None	None	None	None	N
I/S	0.1723	likely_benign	0.1977	benign	-2.371	Highly Destabilizing	0.012	N	0.599	neutral	N	0.464603927	None	None	N
I/T	0.0895	likely_benign	0.1008	benign	-2.16	Highly Destabilizing	None	N	0.369	neutral	N	0.462548161	None	None	N
I/V	0.0658	likely_benign	0.0703	benign	-1.425	Destabilizing	None	N	0.231	neutral	N	0.443847757	None	None	N
I/W	0.6852	likely_pathogenic	0.764	pathogenic	-1.633	Destabilizing	0.864	D	0.671	neutral	None	None	None	None	N
I/Y	0.4058	ambiguous	0.4215	ambiguous	-1.396	Destabilizing	0.356	N	0.653	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.