TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23281	70066;70067;70068	chr2:178576291;178576290;178576289	chr2:179441018;179441017;179441016
N2AB	21640	65143;65144;65145	chr2:178576291;178576290;178576289	chr2:179441018;179441017;179441016
N2A	20713	62362;62363;62364	chr2:178576291;178576290;178576289	chr2:179441018;179441017;179441016
N2B	14216	42871;42872;42873	chr2:178576291;178576290;178576289	chr2:179441018;179441017;179441016
Novex-1	14341	43246;43247;43248	chr2:178576291;178576290;178576289	chr2:179441018;179441017;179441016
Novex-2	14408	43447;43448;43449	chr2:178576291;178576290;178576289	chr2:179441018;179441017;179441016
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: Fn3-57
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.3906
• 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/R	None	None	0.085	N	0.236	0.18	0.306695030598	gnomAD-4.0.0	1.62571E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.90298E-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	0.4354	ambiguous	0.4272	ambiguous	-0.779	Destabilizing	0.944	D	0.54	neutral	None	None	None	None	N
K/C	0.6949	likely_pathogenic	0.6789	pathogenic	-0.86	Destabilizing	0.999	D	0.752	deleterious	None	None	None	None	N
K/D	0.8251	likely_pathogenic	0.8181	pathogenic	-0.607	Destabilizing	0.992	D	0.761	deleterious	None	None	None	None	N
K/E	0.2882	likely_benign	0.2883	benign	-0.434	Destabilizing	0.928	D	0.449	neutral	N	0.479517769	None	None	N
K/F	0.8529	likely_pathogenic	0.8453	pathogenic	-0.212	Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	N
K/G	0.6892	likely_pathogenic	0.6828	pathogenic	-1.208	Destabilizing	0.983	D	0.632	neutral	None	None	None	None	N
K/H	0.4547	ambiguous	0.4454	ambiguous	-1.458	Destabilizing	0.998	D	0.741	deleterious	None	None	None	None	N
K/I	0.3493	ambiguous	0.3363	benign	0.366	Stabilizing	0.989	D	0.807	deleterious	N	0.486652337	None	None	N
K/L	0.3257	likely_benign	0.3132	benign	0.366	Stabilizing	0.983	D	0.632	neutral	None	None	None	None	N
K/M	0.2261	likely_benign	0.2159	benign	0.12	Stabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
K/N	0.6003	likely_pathogenic	0.5967	pathogenic	-0.984	Destabilizing	0.978	D	0.633	neutral	N	0.474673694	None	None	N
K/P	0.6683	likely_pathogenic	0.6482	pathogenic	0.013	Stabilizing	0.997	D	0.777	deleterious	None	None	None	None	N
K/Q	0.1928	likely_benign	0.1913	benign	-0.906	Destabilizing	0.978	D	0.615	neutral	N	0.472899267	None	None	N
K/R	0.0982	likely_benign	0.0951	benign	-0.879	Destabilizing	0.085	N	0.236	neutral	N	0.514441206	None	None	N
K/S	0.6731	likely_pathogenic	0.6743	pathogenic	-1.583	Destabilizing	0.944	D	0.555	neutral	None	None	None	None	N
K/T	0.3089	likely_benign	0.3205	benign	-1.182	Destabilizing	0.978	D	0.669	neutral	N	0.515998644	None	None	N
K/V	0.3214	likely_benign	0.313	benign	0.013	Stabilizing	0.992	D	0.757	deleterious	None	None	None	None	N
K/W	0.8672	likely_pathogenic	0.8503	pathogenic	-0.139	Destabilizing	0.999	D	0.746	deleterious	None	None	None	None	N
K/Y	0.7766	likely_pathogenic	0.7641	pathogenic	0.146	Stabilizing	0.997	D	0.759	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.