TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7884	23875;23876;23877	chr2:178719992;178719991;178719990	chr2:179584719;179584718;179584717
N2AB	7567	22924;22925;22926	chr2:178719992;178719991;178719990	chr2:179584719;179584718;179584717
N2A	6640	20143;20144;20145	chr2:178719992;178719991;178719990	chr2:179584719;179584718;179584717
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-63
• Domain position: 90
• Structural Position: 175
• Q(SASA): 0.3548
• 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	rs1180482059	-0.397	0.193	N	0.409	0.196	0.412064437402	gnomAD-2.1.1	4.13E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.38E-05	None	0	0	0
T/I	rs1180482059	-0.397	0.193	N	0.409	0.196	0.412064437402	gnomAD-4.0.0	2.74767E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.02053E-07	3.51725E-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	0.0805	likely_benign	0.0812	benign	-0.788	Destabilizing	0.09	N	0.324	neutral	N	0.519071527	None	None	N
T/C	0.4739	ambiguous	0.4283	ambiguous	-0.408	Destabilizing	0.944	D	0.421	neutral	None	None	None	None	N
T/D	0.3144	likely_benign	0.3058	benign	0.321	Stabilizing	0.241	N	0.417	neutral	None	None	None	None	N
T/E	0.2429	likely_benign	0.2496	benign	0.283	Stabilizing	0.241	N	0.407	neutral	None	None	None	None	N
T/F	0.2216	likely_benign	0.2059	benign	-1.091	Destabilizing	0.818	D	0.503	neutral	None	None	None	None	N
T/G	0.2642	likely_benign	0.2433	benign	-0.974	Destabilizing	0.116	N	0.457	neutral	None	None	None	None	N
T/H	0.1725	likely_benign	0.1672	benign	-1.311	Destabilizing	0.818	D	0.468	neutral	None	None	None	None	N
T/I	0.1906	likely_benign	0.1771	benign	-0.398	Destabilizing	0.193	N	0.409	neutral	N	0.519034241	None	None	N
T/K	0.1612	likely_benign	0.1722	benign	-0.402	Destabilizing	0.241	N	0.396	neutral	None	None	None	None	N
T/L	0.1037	likely_benign	0.0994	benign	-0.398	Destabilizing	0.116	N	0.409	neutral	None	None	None	None	N
T/M	0.0911	likely_benign	0.0918	benign	-0.035	Destabilizing	0.818	D	0.439	neutral	None	None	None	None	N
T/N	0.0986	likely_benign	0.0925	benign	-0.202	Destabilizing	0.006	N	0.285	neutral	N	0.494175869	None	None	N
T/P	0.4489	ambiguous	0.4338	ambiguous	-0.499	Destabilizing	0.773	D	0.458	neutral	D	0.527109214	None	None	N
T/Q	0.1699	likely_benign	0.1776	benign	-0.46	Destabilizing	0.019	N	0.271	neutral	None	None	None	None	N
T/R	0.1262	likely_benign	0.1306	benign	-0.201	Destabilizing	0.241	N	0.442	neutral	None	None	None	None	N
T/S	0.0925	likely_benign	0.0853	benign	-0.57	Destabilizing	0.001	N	0.087	neutral	N	0.451366454	None	None	N
T/V	0.1602	likely_benign	0.1469	benign	-0.499	Destabilizing	0.008	N	0.178	neutral	None	None	None	None	N
T/W	0.517	ambiguous	0.4789	ambiguous	-0.965	Destabilizing	0.981	D	0.534	neutral	None	None	None	None	N
T/Y	0.2211	likely_benign	0.2051	benign	-0.725	Destabilizing	0.818	D	0.504	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.