Submissions for variant NM_198525.3(KIF7):c.3784C>T (p.Arg1262Trp)

gnomAD frequency: 0.00022  dbSNP: rs142598777

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000808133	SCV000948225	uncertain significance	Acrocallosal syndrome	2023-12-11	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1262 of the KIF7 protein (p.Arg1262Trp). This variant is present in population databases (rs142598777, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with KIF7-related conditions. ClinVar contains an entry for this variant (Variation ID: 652558). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt KIF7 protein function with a negative predictive value of 80%. 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.
Illumina Laboratory Services, Illumina	RCV000808133	SCV001274859	uncertain significance	Acrocallosal syndrome	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.
GeneDx	RCV001553033	SCV001773830	likely benign	not provided	2020-01-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002537282	SCV003721719	uncertain significance	Inborn genetic diseases	2022-05-05	criteria provided, single submitter	clinical testing	The c.3784C>T (p.R1262W) alteration is located in exon 19 (coding exon 18) of the KIF7 gene. This alteration results from a C to T substitution at nucleotide position 3784, causing the arginine (R) at amino acid position 1262 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity	RCV001553033	SCV003810056	uncertain significance	not provided	2019-04-23	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003147555	SCV003835996	uncertain significance	Hydrolethalus syndrome 2	2022-10-31	criteria provided, single submitter	clinical testing