Submissions for variant NM_001136193.2(FASTKD2):c.911T>C (p.Ile304Thr)

gnomAD frequency: 0.00012  dbSNP: rs144499152

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000199763	SCV000251392	likely pathogenic	not provided	2012-09-04	criteria provided, single submitter	clinical testing	This variant is denoted c.911 T>C at the cDNA level or p.Ile304Thr (I304T) at the protein level. The I304T missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The amino acid change is nonconservative in that a non-polar Isoleucine residue is replaced by a polar Threonine residue. This change occurs at a highly conserved position in the FASTKD2 protein, and multiple in-silico analysis programs predict that I304T is damaging to the FASTKD2 protein. Therefore, I304T is a strong candidate for a disease-causing mutation, however the possibility that it is a benign variant cannot be excluded. The variant is found in MITONUC-MITOP panel(s).
Eurofins Ntd Llc (ga)	RCV000401064	SCV000336666	benign	not specified	2015-10-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001139103	SCV001299214	uncertain significance	Cytochrome-c oxidase deficiency disease	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae	RCV000199763	SCV002447613	benign	not provided	2023-03-18	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003967517	SCV004782055	likely benign	FASTKD2-related condition	2020-03-27	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).