TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21523	64792;64793;64794	chr2:178585177;178585176;178585175	chr2:179449904;179449903;179449902
N2AB	19882	59869;59870;59871	chr2:178585177;178585176;178585175	chr2:179449904;179449903;179449902
N2A	18955	57088;57089;57090	chr2:178585177;178585176;178585175	chr2:179449904;179449903;179449902
N2B	12458	37597;37598;37599	chr2:178585177;178585176;178585175	chr2:179449904;179449903;179449902
Novex-1	12583	37972;37973;37974	chr2:178585177;178585176;178585175	chr2:179449904;179449903;179449902
Novex-2	12650	38173;38174;38175	chr2:178585177;178585176;178585175	chr2:179449904;179449903;179449902
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-124
• Domain position: 55
• Structural Position: 137
• Q(SASA): 0.2703
• Predicted PPI site: I

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/V	rs761550336	-1.269	None	N	0.117	0.16	0.246215685461	gnomAD-2.1.1	8.06E-06	None	None	None	None	I	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
I/V	rs761550336	-1.269	None	N	0.117	0.16	0.246215685461	gnomAD-4.0.0	1.11455E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86044E-06	7.16764E-05	3.02663E-05

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	0.3546	ambiguous	0.4033	ambiguous	-2.687	Highly Destabilizing	0.007	N	0.373	neutral	None	None	None	None	I
I/C	0.6369	likely_pathogenic	0.6705	pathogenic	-1.897	Destabilizing	0.356	N	0.522	neutral	None	None	None	None	I
I/D	0.8276	likely_pathogenic	0.8459	pathogenic	-3.04	Highly Destabilizing	0.136	N	0.593	neutral	None	None	None	None	I
I/E	0.7287	likely_pathogenic	0.7421	pathogenic	-2.864	Highly Destabilizing	0.136	N	0.542	neutral	None	None	None	None	I
I/F	0.21	likely_benign	0.221	benign	-1.645	Destabilizing	0.055	N	0.439	neutral	N	0.464351607	None	None	I
I/G	0.6961	likely_pathogenic	0.7416	pathogenic	-3.18	Highly Destabilizing	0.136	N	0.536	neutral	None	None	None	None	I
I/H	0.5952	likely_pathogenic	0.6307	pathogenic	-2.559	Highly Destabilizing	0.864	D	0.566	neutral	None	None	None	None	I
I/K	0.6238	likely_pathogenic	0.6383	pathogenic	-2.082	Highly Destabilizing	0.136	N	0.536	neutral	None	None	None	None	I
I/L	0.1359	likely_benign	0.1317	benign	-1.273	Destabilizing	None	N	0.115	neutral	N	0.421888909	None	None	I
I/M	0.1179	likely_benign	0.1239	benign	-1.147	Destabilizing	0.171	N	0.467	neutral	N	0.473856525	None	None	I
I/N	0.3512	ambiguous	0.3683	ambiguous	-2.297	Highly Destabilizing	0.295	N	0.612	neutral	N	0.447478	None	None	I
I/P	0.9718	likely_pathogenic	0.9717	pathogenic	-1.725	Destabilizing	0.628	D	0.613	neutral	None	None	None	None	I
I/Q	0.5722	likely_pathogenic	0.6107	pathogenic	-2.252	Highly Destabilizing	0.628	D	0.586	neutral	None	None	None	None	I
I/R	0.5331	ambiguous	0.5473	ambiguous	-1.637	Destabilizing	0.356	N	0.605	neutral	None	None	None	None	I
I/S	0.3059	likely_benign	0.3364	benign	-2.951	Highly Destabilizing	0.012	N	0.483	neutral	N	0.379058065	None	None	I
I/T	0.1941	likely_benign	0.2344	benign	-2.649	Highly Destabilizing	None	N	0.236	neutral	N	0.374110818	None	None	I
I/V	0.0605	likely_benign	0.0679	benign	-1.725	Destabilizing	None	N	0.117	neutral	N	0.376636622	None	None	I
I/W	0.8531	likely_pathogenic	0.8755	pathogenic	-2.022	Highly Destabilizing	0.864	D	0.595	neutral	None	None	None	None	I
I/Y	0.5343	ambiguous	0.5257	ambiguous	-1.79	Destabilizing	0.356	N	0.558	neutral	None	None	None	None	I

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.