Submissions for variant NM_005334.3(HCFC1):c.4983_4988del (p.Val1662_Thr1663del)

dbSNP: rs1275942023

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000599399	SCV000710089	uncertain significance	not provided	2024-07-26	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In-frame deletion of 2 amino acids in a non-repeat region; In silico analysis indicates that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
CeGaT Center for Human Genetics Tuebingen	RCV000599399	SCV001150500	uncertain significance	not provided	2019-02-01	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV001262125	SCV001439887	uncertain significance	Methylmalonic acidemia with homocystinuria, type cblX	2019-01-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001262125	SCV002116056	uncertain significance	Methylmalonic acidemia with homocystinuria, type cblX	2021-09-17	criteria provided, single submitter	clinical testing	This variant, c.4983_4988del, results in the deletion of 2 amino acid(s) of the HCFC1 protein (p.Val1662_Thr1663del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with HCFC1-related conditions. ClinVar contains an entry for this variant (Variation ID: 503794). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV002532688	SCV003667756	uncertain significance	Inborn genetic diseases	2022-10-18	criteria provided, single submitter	clinical testing	The c.4983_4988delCGTGAC (p.V1662_T1663del) alteration is located in exon 20 (coding exon 20) of the HCFC1 gene. This alteration consists of an in-frame deletion of 6 nucleotides between nucleotide positions c.4983 and c.4988, resulting in the deletion of 2 residues. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Breakthrough Genomics, Breakthrough Genomics	RCV000599399	SCV005192349	uncertain significance	not provided		criteria provided, single submitter	not provided