TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25116	75571;75572;75573	chr2:178570786;178570785;178570784	chr2:179435513;179435512;179435511
N2AB	23475	70648;70649;70650	chr2:178570786;178570785;178570784	chr2:179435513;179435512;179435511
N2A	22548	67867;67868;67869	chr2:178570786;178570785;178570784	chr2:179435513;179435512;179435511
N2B	16051	48376;48377;48378	chr2:178570786;178570785;178570784	chr2:179435513;179435512;179435511
Novex-1	16176	48751;48752;48753	chr2:178570786;178570785;178570784	chr2:179435513;179435512;179435511
Novex-2	16243	48952;48953;48954	chr2:178570786;178570785;178570784	chr2:179435513;179435512;179435511
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-134
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.5788
• 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/Q	rs900765170	None	0.983	N	0.722	0.248	0.277730125212	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/Q	rs900765170	None	0.983	N	0.722	0.248	0.277730125212	gnomAD-4.0.0	2.03E-06	None	None	None	None	N	None	3.49553E-05	0	None	0	0	None	0	0	0	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	0.2614	likely_benign	0.2649	benign	-0.483	Destabilizing	0.845	D	0.627	neutral	None	None	None	None	N
K/C	0.5964	likely_pathogenic	0.638	pathogenic	-0.445	Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
K/D	0.6076	likely_pathogenic	0.6262	pathogenic	-0.171	Destabilizing	0.975	D	0.73	prob.delet.	None	None	None	None	N
K/E	0.2098	likely_benign	0.2233	benign	-0.065	Destabilizing	0.892	D	0.631	neutral	N	0.480528994	None	None	N
K/F	0.7097	likely_pathogenic	0.7502	pathogenic	-0.252	Destabilizing	0.987	D	0.755	deleterious	None	None	None	None	N
K/G	0.4451	ambiguous	0.4564	ambiguous	-0.808	Destabilizing	0.975	D	0.659	neutral	None	None	None	None	N
K/H	0.3178	likely_benign	0.3307	benign	-1.008	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
K/I	0.2623	likely_benign	0.2901	benign	0.348	Stabilizing	0.967	D	0.759	deleterious	N	0.497160766	None	None	N
K/L	0.3065	likely_benign	0.3363	benign	0.348	Stabilizing	0.845	D	0.643	neutral	None	None	None	None	N
K/M	0.2153	likely_benign	0.2399	benign	0.006	Stabilizing	0.999	D	0.76	deleterious	None	None	None	None	N
K/N	0.4506	ambiguous	0.4868	ambiguous	-0.378	Destabilizing	0.967	D	0.713	prob.delet.	N	0.513025415	None	None	N
K/P	0.839	likely_pathogenic	0.8398	pathogenic	0.1	Stabilizing	0.987	D	0.771	deleterious	None	None	None	None	N
K/Q	0.1358	likely_benign	0.1363	benign	-0.365	Destabilizing	0.983	D	0.722	prob.delet.	N	0.505656725	None	None	N
K/R	0.0739	likely_benign	0.075	benign	-0.441	Destabilizing	0.892	D	0.624	neutral	D	0.532227251	None	None	N
K/S	0.3855	ambiguous	0.4047	ambiguous	-0.89	Destabilizing	0.845	D	0.632	neutral	None	None	None	None	N
K/T	0.1776	likely_benign	0.1857	benign	-0.589	Destabilizing	0.025	N	0.431	neutral	D	0.532227251	None	None	N
K/V	0.2439	likely_benign	0.2629	benign	0.1	Stabilizing	0.95	D	0.652	neutral	None	None	None	None	N
K/W	0.7484	likely_pathogenic	0.7787	pathogenic	-0.236	Destabilizing	0.999	D	0.74	deleterious	None	None	None	None	N
K/Y	0.5879	likely_pathogenic	0.6338	pathogenic	0.047	Stabilizing	0.996	D	0.753	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.