TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24034	72325;72326;72327	chr2:178574032;178574031;178574030	chr2:179438759;179438758;179438757
N2AB	22393	67402;67403;67404	chr2:178574032;178574031;178574030	chr2:179438759;179438758;179438757
N2A	21466	64621;64622;64623	chr2:178574032;178574031;178574030	chr2:179438759;179438758;179438757
N2B	14969	45130;45131;45132	chr2:178574032;178574031;178574030	chr2:179438759;179438758;179438757
Novex-1	15094	45505;45506;45507	chr2:178574032;178574031;178574030	chr2:179438759;179438758;179438757
Novex-2	15161	45706;45707;45708	chr2:178574032;178574031;178574030	chr2:179438759;179438758;179438757
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-131
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.6396
• 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
K/T	None	None	0.062	N	0.437	0.183	0.223146558224	gnomAD-4.0.0	1.59204E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85945E-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
K/A	0.2604	likely_benign	0.2688	benign	-0.52	Destabilizing	0.035	N	0.441	neutral	None	None	None	None	N
K/C	0.6224	likely_pathogenic	0.6053	pathogenic	-0.668	Destabilizing	0.935	D	0.507	neutral	None	None	None	None	N
K/D	0.5147	ambiguous	0.5104	ambiguous	-0.246	Destabilizing	0.149	N	0.44	neutral	None	None	None	None	N
K/E	0.2163	likely_benign	0.2204	benign	-0.149	Destabilizing	0.062	N	0.485	neutral	N	0.4996134	None	None	N
K/F	0.7063	likely_pathogenic	0.7075	pathogenic	-0.449	Destabilizing	0.555	D	0.495	neutral	None	None	None	None	N
K/G	0.4432	ambiguous	0.4393	ambiguous	-0.803	Destabilizing	0.149	N	0.441	neutral	None	None	None	None	N
K/H	0.2605	likely_benign	0.2584	benign	-0.872	Destabilizing	0.555	D	0.435	neutral	None	None	None	None	N
K/I	0.2618	likely_benign	0.2726	benign	0.189	Stabilizing	0.484	N	0.497	neutral	N	0.517226804	None	None	N
K/L	0.283	likely_benign	0.2827	benign	0.189	Stabilizing	0.149	N	0.456	neutral	None	None	None	None	N
K/M	0.1906	likely_benign	0.1942	benign	-0.226	Destabilizing	0.935	D	0.439	neutral	None	None	None	None	N
K/N	0.3448	ambiguous	0.3529	ambiguous	-0.492	Destabilizing	0.117	N	0.437	neutral	N	0.507022162	None	None	N
K/P	0.5923	likely_pathogenic	0.5684	pathogenic	-0.02	Destabilizing	0.555	D	0.402	neutral	None	None	None	None	N
K/Q	0.1304	likely_benign	0.1347	benign	-0.481	Destabilizing	0.117	N	0.459	neutral	N	0.477851516	None	None	N
K/R	0.0754	likely_benign	0.0754	benign	-0.3	Destabilizing	None	N	0.296	neutral	N	0.480965388	None	None	N
K/S	0.3404	ambiguous	0.3448	ambiguous	-0.987	Destabilizing	0.003	N	0.256	neutral	None	None	None	None	N
K/T	0.1438	likely_benign	0.1481	benign	-0.701	Destabilizing	0.062	N	0.437	neutral	N	0.492993256	None	None	N
K/V	0.2779	likely_benign	0.2861	benign	-0.02	Destabilizing	0.38	N	0.429	neutral	None	None	None	None	N
K/W	0.7006	likely_pathogenic	0.6868	pathogenic	-0.452	Destabilizing	0.935	D	0.567	neutral	None	None	None	None	N
K/Y	0.5412	ambiguous	0.5465	ambiguous	-0.145	Destabilizing	0.555	D	0.482	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.